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)

The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose-dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters.
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PMID:Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. 220 49

The growth inhibitory effects of interferons, IFN-alpha and IFN-gamma on human lung cancer cell lines were studied using both a tetrazolium (MTT) colorimetric assay and direct cell counting. Significant discrepancies between the two assays were observed, the MTT assay consistently underestimating the growth inhibitory effects of the IFNs. There was no direct chemical effect of the IFNs on the tetrazolium reduction process. IFN treated cells showed increased cell size compared with control cells, although there was little or no change in cell cycle distribution. Mitochondrial activity was 30-50% greater in IFN-gamma treated cells (COR-L23) than the controls. Reduced formazan production per cell was observed in medium which had supported cell growth for several days. Differential 'medium conditioning' led to a difference in formazan production per cell between IFN and control cells and this was the major basis of the observed discrepancy. This discrepancy was not due to the differences in the glucose concentrations between these media. However, differences in pH between the media proved to be the major contributory factor of the discrepancy.
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PMID:The MTT assay underestimates the growth inhibitory effects of interferons. 252 90

A range of anthracyclines and related compounds were evaluated for activity against murine and human cell lines exhibiting multidrug resistance (MDR). Cell lines used were the NCI-H69 human small-cell lung cancer line and the EMT6 murine mammary tumour line, together with their multidrug-resistant counterparts produced by in vitro exposure to Adriamycin (ADM). Chemosensitivity testing was carried out using the tetrazolium (MTT) dye assay. Results were expressed as the ratio of the ID50 for the resistant line to that obtained in the parent, i.e. the resistance factor (RF). Compounds exhibiting much lower RF values than ADM in both resistant cell lines were identified as those anthracyclines with 9-alkyl substituents and those with certain changes to the amino sugar residue at position 3' and 4', together with the anthracenedione mitoxantrone (MIT). In a further attempt to overcome resistance, we used four of these compounds, Ro 31-1215, 4'-deoxy-4'-iodo-ADM (iodo-ADM), aclacinomycin A (ACL) and MIT (all yielding low RF values), in combination with the resistance modifiers verapamil (VRP) and cyclosporin A (CYA). Additional enhancement of chemosensitivity was achieved in the ADM-resistant sublines, as shown by the further decrease in RF values. At the concentrations used, the largest effects were generally seen with CYA, and the combination of this modifier with ACL and MIT was particularly effective. For the H69/LX4 resistant line, the latter combinations gave RF values approaching unity. These findings point to the use of analogues with the 9-alkyl substituent and/or specific changes to the sugar residue in combination with resistance modifiers as a therapeutic strategy for circumvention of the MDR phenotype.
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PMID:Identification of anthracyclines and related agents that retain preferential activity over adriamycin in multidrug-resistant cell lines, and further resistance modification by verapamil and cyclosporin A. 254 27

Claims of synergy between etoposide and cisplatin have been based upon preclinical in vivo murine P388 models or upon human clinical trials in tumors such as lung cancer. Such in vivo studies are useful in exploring therapeutic synergy, i.e., an improved therapeutic strategy. The term "synergy" in this context is sometimes, however, taken to imply greater than additive kill of tumor cells. Unfortunately, it is virtually impossible to document supra-additive tumor cell kill in vivo, since in vivo curves of therapeutic effect are not linear and drugs are therefore not additive with themselves. Therapeutic synergy may, in fact, occur when two drugs are merely additive (or even antagonistic) with regard to cytotoxicity if the drugs have nonoverlapping host toxicity. The demonstration of true supra-additive cell kill would imply an interaction of the two agents at a cellular level and would have profound implications for biochemical studies. In order to determine whether the reported therapeutic synergy of etoposide and cisplatin is due, in part, to supra-additive cell kill, we used an in vitro tetrazolium-based colorimetric assay for cytotoxicity (MTT assay) and an isobologram analysis to test combinations of the two drugs against four human small cell and four human non-small cell lung carcinoma lines. Using a rigorous test for in vitro synergy, we could not establish a greater than additive cytotoxic effect on our cell lines. It thus appears that the clinical synergy between etoposide and cisplatin is not due to a supra-additive effect at the cellular level. Our results have implications for a variety of fields in which claims of "synergy" often appear.
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PMID:Lack of in vitro synergy between etoposide and cis-diamminedichloroplatinum(II). 270 26

Thirty human lung cancer cell lines were tested for chemosensitivity using the semi-automated, non-clonogenic MTT assay. The tumour cell lines came from three major categories of patients: untreated small cell lung cancer (SCLC); SCLC relapsing on chemotherapy; and non-SCLC predominantly from untreated patients. From these data IC50 values were derived for each drug in each cell line. While some inter-experimental variability was observed, the rank order of chemosensitivity of each cell line within this panel was significantly correlated between experiments. These results show that tumour cell lines derived from untreated small cell lung cancer patients were the most chemosensitive for adriamycin, melphalan, vincristine and VP16 compared to the other cell types. In addition, untreated SCLC was more sensitive than non-SCLC to BCNU and cis-platin, while vincristine was the only drug to which treated SCLC was more sensitive compared to the non-SCLC lines. In contrast, no significant differences between the lung cancer types were observed for vinblastine. Thus, this panel of lung cancer cells exhibited a drug sensitivity profile paralleling that observed in clinical practice. These results suggest that this lung cancer cell line panel in combination with a relatively simple but reproducible chemosensitivity assay, such as the MTT assay, has potential for the testing of drug combinations and evaluating new anti-cancer agents in vitro.
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PMID:Chemosensitivity testing of human lung cancer cell lines using the MTT assay. 284 61

Seven small- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cytotoxicity of cytotoxic drugs such as (1aS-(1a alpha,8 beta,8a alpha,8b alpha]-8-[aminocarbonyl)oxy)methyl)-4,8a- dimethoxy-1,1a,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6- nitrosoazirino(2',3':3,4)-pyrrolo-(1,2-a)indole (RM-49) and 11-acetyl-8-carboxymethyl-4-formyl-14oxa-1,11-diaze- tetracyclo(7.4.1.0(2,7),0(10,12]tetradeca-2-4-6-trien-6,9-++ +diyl-diacetate (FK973). In vitro cytotoxicities of RM-49 and FK973 were compared with those of mitomycin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS). Drug sensitivity was determined using a tetrazolium (MTT)-based assay. Average IC50 values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration. The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) = -0.788 + (0.755 x log(LD50], and relative antitumor activity, RAA (PPC/IC50), of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05). Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted.
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PMID:In vitro antitumor activity of mitomycin C derivative (RM-49) and new anticancer antibiotics (FK973) against lung cancer cell lines determined by tetrazolium dye (MTT) assay. 284 80

In order to analyze the presence and the function of the "insulin-like growth factor I (IGF-I) system" in human non-small-cell lung cancer (N-SCLC) we tested 5 cell lines of different histological sub-types: A549, Ca-Lu-6, SK-Lu-1 (adenocarcinoma); Ca-Lu-1, SK-Mes-1 (squamous carcinoma) and one normal fibroblast-like fetal lung cell line (IMR-90) for expression of the IGF-I peptide and its RNA transcribed from the IGF-I gene; IGF-binding proteins (IGF-BP); IGF-I receptor (IGF-I-R) and its mRNA. In addition, we examined the capacity of exogenous human recombinant IGF-I to enhance the in vitro cell proliferation. In medium conditioned from cell cultures, we detected immunoreactive IGF-I material by radioimmunoassay. Western ligand blot and affinity labelling demonstrated the presence of several molecular species of IGF-BPs (IGF-BP-4, -1, -2, -3) as well. Northern blot analysis of polyA+ RNA from all cell lines examined revealed the presence of IGF-I and IGF-I-R mRNA. Moreover, binding studies on cultured cell lines showed one class of high-affinity, operative type-I IGF cell-surface binding sites. Finally, by thymidine uptake and colorimetric metabolic MTT assays, we found that most neoplastic cell lines react mitogenically to IGF-I and that its physiological effect is abolished by an anti-IGF-I-receptor antibody. These data indicate the importance of the IGF-I system in N-SCLC growth. Furthermore, they suggest that this mitogenic complex should be appraised as a possible target for anti-neoplastic drugs, antibodies or growth-factor analogues offering potential new approaches to therapy.
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PMID:Expression and function of the insulin-like growth factor I system in human non-small-cell lung cancer and normal lung cell lines. 750 79

Type I and type II cAMP receptor proteins participate in cell growth regulation, differentiation and neoplastic transformation of neoplasms. In this paper the growth regulatory effects of cAMP analogs, DBcAMP (non-site-selective) and 8-Cl-cAMP (site-selective) on a highly metastatic human lung cancer cell line PG were studied. By MTT assay, DBcAMP at 1mmol/L was found to inhibit PG growth by 30% on the day 8, while 8-CL-cAMP at 10-20 mumol/L inhibited the growth by 75%-80%. When phosphodiesterase inhibitor isobutyl-1-methyl-xanthine (IBMX) was added the inhibitory effect of 8-Cl-cAMP was not enhanced, whereas that of DBcAMP was significantly enhanced. The invasiveness and colony-forming ability of the treated cells decreased. The cAMP level as determined by RIA was much more increased in DBcAMP-treated than in 8-Cl-cAMP-treated PG cells. The result suggests that 8-Cl-cAMP and DBcAMP exert their effects on tumor cell growth and invasion by defferent mechanisms.
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PMID:[Effects of site-selective 8-Cl-cAMP on the growth regulation of human lung giant cell cancer]. 765 98

We have characterised an etoposide-resistant subline of the small-cell lung cancer cell line, UMCC-1, derived at our centre. Subline UMCC-1/VP was developed by culturing the parent line in increasing concentrations of etoposide over 16 months. UMCC-1/VP is 20-fold resistant to etoposide by MTT assays, relative to the parent line, and is cross-resistant to doxorubicin, vincristine and actinomycin D, but not to taxol, cisplatin, melphalan, thiotepa or idarubicin. Topoisomerase II immunoblotting demonstrates a 50% reduction of the protein in the resistant subline. The UMCC-1/VP subline demonstrates a marked decrease in the accumulation of [3H]etoposide relative to the parent line, as well as a modest reduction in the accumulation of daunorubicin. Reverse transcription-polymerase chain reaction assays demonstrate no detectable mdr1 expression but marked expression of the multidrug resistance-associated protein (MRP) gene in the resistant subline. Northern blotting with an MRP cDNA probe confirms marked overexpression of the MRP gene only in the UMCC-1/VP subline. Western blotting with antisera against MRP peptide confirms a 195 kDa protein band in the UMCC-1/VP subline. Southern blotting experiments demonstrate a 10-fold amplification of the MRP gene in the resistant subline. Depletion of glutathione with buthionine sulphoximine sensitised UMCC-1/VP cells to daunorubicin and etoposide. Our studies indicate that MRP gene expression may be induced by etoposide and may lead to reduced accumulation of the drug.
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PMID:An etoposide-resistant lung cancer subline overexpresses the multidrug resistance-associated protein. 766 58

Suramin cytotoxicity was studied in a panel of human lung cancer cell lines by the MTT assay. The concentrations of suramin which induced 50% growth inhibition (IC50) ranged from 130 to 3715 microM for the cell lines growing in medium containing 10% fetal calf serum (FCS). In only one cell line was the IC50 at a concentration that can be reached in plasma of patients treated with suramin. Suramin was 18 and 3.3 times more cytotoxic on NCI-N417 cells growing in 2% FCS and in HITES serum-free medium, respectively, than growing in 10% FCS. No difference in suramin cytotoxicity was observed between small and non-small cell lung cancer cell lines. At the lower concentrations tested, suramin stimulated proliferation of the two small cell lung cancer cell lines, NCI-H187 and NCI-N417. Of several growth factors tested, none induced stimulation of growth in NCI-H187 and NCI-N417 cell lines, nor did they in any way alter the stimulatory effect of suramin. Cell counting, DNA flow cytometric analysis and Ki-67 staining confirmed a higher proliferative state in suramin-exposed NCI-H187 cells as compared with untreated cells. However, topoisomerase II-alpha gene expression remained unchanged, as assessed by northern blot analysis and immunostaining. Suramin had an inhibitory effect on topoisomerase II activity, as assessed by the kDNA decatenation assay, with an IC50 of approximately 40 microM. In conclusion, suramin has significant cytotoxic activity in a minority of human lung cancer cell lines, and it stimulates proliferation in some instances. The pleiotropic action of suramin observed should caution on the possibility of tumour acceleration in patients being treated with this drug.
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PMID:Effects of suramin on human lung cancer cell lines. 771 32


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