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Query: UMLS:C0007131 (non-small cell lung cancer)
 22,601 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The schedule-dependent interaction of paclitaxel and doxorubicin was evaluated in four human cancer cell lines. The cells were exposed simultaneously or sequentially to the two agents for 24 h, and were then incubated in drug-free medium for 4 and 3 days, respectively. The cell growth inhibitions were determined by the MTT assay. The cytotoxic interactions at the IC80 level were evaluated by the isobologram method of Steel and Peckham. In non-small cell lung cancer A549, breast cancer MCF7 and colon cancer WiDr cells, antagonistic effects were observed for the paclitaxel and doxorubicin combination on simultaneous exposure to the two agents and on sequential exposure to doxorubicin followed by paclitaxel, while additive effects were observed for the combination on sequential exposure to paclitaxel followed by doxorubicin. In ovarian cancer PA1 cells, additive effects were observed for all schedules. These findings suggest that sequential administration of paclitaxel followed by doxorubicin may be the most suitable sequence, while the simultaneous administration of the two agents and the sequential administration of doxorubicin followed by paclitaxel may result in less tumour cell kill than anticipated. Further preclinical and clinical studies are required to elucidate the relationship between paclitaxel and doxorubicin with regard to both antitumour activity and toxicity.
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PMID:Schedule-dependent interaction between paclitaxel and doxorubicin in human cancer cell lines in vitro. 865 67

The retinoblastoma gene product (RB protein) plays a key role in the progression of the cell cycle from G1 to S phase in normal and neoplastic cells. The activity of RB is regulated by phosphorylation and dephosphorylation with cell-cycle-dependent protein kinases. We investigated the effect of the protein kinase inhibitors, staurosporine and 7-hydroxy-staurosporine (UCN-01), on RB protein expression of N417 small cell lung cancer cells (absent RB), H209 small cell lung cancer cells (mutant RB), and Ma-31 non-small cell lung cancer cells (wild-type RB), using immunologic blotting. Staurosporine and UCN-01 each suppressed the growth of N417, H209 and Ma-31 cells in a dose-dependent manner in MTT assay. IC50 values of staurosporine for N417, H209 and Ma-31 cells were 54, 29 and 602 nM, respectively. IC50 values of UCN-01 for N417, H209 and Ma-31 cells were 737, 181 and 2,197 nM, respectively. Exposure to staurosporine and UCN-01 for 72 h each suppressed the level of expression and altered the ratio of phosphorylated/dephosphorylated RB protein (ppRB/pRB) of Ma-31 cells. Conversely, these agents increased the expression level of RB protein at concentrations less than IC50, and did not change phosphorylation status of mutant RB protein of H209 cells at the concentrations studied. A time course study demonstrated that exposure to the IC50 concentration of staurosporine for 48-72 h increased the ratio of ppRB/ pRB of Ma-31 cells, while exposure to the IC50 concentration of UCN-01 decreased that ratio. UCN-01 increased % cells in G2 + M phase and decreased % cells in S phase, while staurosporine increased % cells in G1 phase and decreased % cells in G2 + M phase. UCN-01 did not induce apoptosis (DNA content < 2 N) of Ma-31 cells, but staurosporine induced it. These findings suggest that the differing effects of staurosporine and UCN-01 on RB protein expression and cell cycle phases of lung cancer cells may explain their differing in vivo antitumor effect of staurosporine and UCN-01 despite their similar chemical structures.
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PMID:Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines. 896 Jan 46

1. The purpose of this study was to investigate the antiproliferative effect and the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non-small cell lung cancer (N-SCLC) cell lines. 2. For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF-I and IGF-binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF-I-receptor level were tested by binding studies on cell monolayers. 3. A significant concentration- and time-dependent cytostatic activity of FCE 26644 (IC50 approximately 200 micrograms ml-1 at 72 h) compared to its analogue FCE 27784 (IC50 > 800 micrograms ml-1) was observed in both cell lines studied. The IGF-I-stimulated proliferation of the IGF-I-responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF-I-like material and reduced the IGF-I binding (IC50 > 100 micrograms ml-1) in both A549 and Ca-Lu-1 cell lines. FCE 26644 (100 micrograms ml-1) did not affect the KD (approximately 0.5 nM) but reduced the Bmax and the number of receptor sites (50%). 4. Our findings demonstrate that the ability to down-regulate the cell proliferation of N-SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the "IGF-I mitogenic system'.
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PMID:Anti-insulin-like growth factor-I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines. 903 61

To determine the optimal combination of commonly used anticancer agents with 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11), for chemotherapy of lung cancer, we studied the effects of SN-38 in combination with six representative anticancer agents on the human small cell lung cancer (SCLC) cell line, NCl N417, and the non-small cell lung cancer (NSCLC) cell line, PC-9. The anticancer activity was evaluated by MTT assay and the effects of drug combinations on ID50 were analyzed by an improved isobologram method. In the SCLC cell line, supra-additive effect was observed for SN-38 in combination with cisplatin, etoposide (VP-16) and paclitaxel (Taxol). An additive effect was observed for its combination with bleomycin. Sub-additive and protective effects were found in combination with adriamycin (ADR) and 5-fluorouracil (5-FU). In the NSCLC cell line, supra-additive and marginal supra-additive effects were found for SN-38 in combination with VP-16, ADR, 5-FU and bleomycin. The others showed additive effects with SN-38. No drug showed sub-additive and protective effects with SN-38. These results suggest that all the drugs we selected can be used with SN-38 simultaneously for NSCLC, while for SCLC, cisplatin, VP-16 and Taxol are the most suitable for combination with SN-38.
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PMID:Effect of CPT-11 in combination with other anticancer agents in lung cancer cells. 909 27

We sought to determine the functional significance of the c-kit receptor (Kit) in melanoma, breast carcinoma, and non-small cell lung cancer (NSCLC). To explore these issues, we first screened cell lines of each type for c-kit mRNA expression using a reverse-transcription polymerase chain reaction. We found that WM-39 melanoma cells, HTB-22 breast carcinoma cells, and A549 NSCLC cells all expressed c-kit mRNA. Of interest, all of these cells expressed the c-kit ligand, Steel factor (SF). We then assessed the functional significance of c-kit and SF expression by disrupting the gene's expression with antisense (AS) oligodeoxynucleotides (ODN) targeted to c-kit mRNA codons 1-6 and SF mRNA codons 2-7, respectively. Nonhybridizing sequences [sense (5) and scrambled (SCR)] were also employed as controls. WM-39, HTB-22, and A549 cells were exposed to ODN (approximately 25 microM) for 5-7 days. Downregulation of c-kit and SF mRNA, and c-kit protein was demonstrated in cells treated with AS ODN. Effects on viable cell growth were demonstrated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -sulfophenyl)- 2H-tetrazolium (MTS) assay. In fact, c-kit antisense ODN inhibited the viable cell growth of A549 cells 66% and 79% compared to sense and untreated controls (P = .0003; P < .0001). Additionally, WM-39 cell growth was inhibited 48% and 21% (P < .0001, P < .03) and HTB-22 cell growth was inhibited 50% (P < .001) compared to sense and untreated controls. Viable cell growth was also significantly inhibited by SF AS ODN compared to S and SCR controls in all cell lines. These results demonstrate that WM-39, HTB-22, and A549 NSCLC cells all express the c-kit and SF protooncogenes and suggest that the encoded receptor and ligand are important for cell growth. By finding the presence, and functional importance, of both the receptor and ligand in these cells, this study suggests the existence of an autocrine loop growth mechanism worthy of further study.
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PMID:Evidence for a functional kit receptor in melanoma, breast, and lung carcinoma cells. 917 36

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.
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PMID:Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained. 938 35

The combined effects of TNP-470, a promising antiangiogenic agent, and SN-38, a camptothecin derivative, were evaluated in four human cultured cell lines derived from non-small cell lung cancer (NSCLC). Cytotoxicity experiments were determined by using a tetrazolium salt (MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentrations on these cell lines were 47.3-139.8 microM. Evaluation of drug interactions with isobologram and the combination index values showed that sequential exposure to SN-38 followed by TNP-470 produced synergistic effects in the four cell lines tested. Our findings suggest that such an angiocytotoxic chemotherapy might be promising for the treatment of NSCLC.
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PMID:Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage of combined effects of TNP-470 and SN-38. 957 59

The effects of TNP-470, one of the promising antiangiogenic agents and taxol when combined were evaluated in two human cultured cell lines derived from non-small cell lung cancer(NSCLC). Cytotoxicity was determined using a tetrazolium salt(MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentration on these cell lines were 50.0 to 62.5 microM. Evaluation of drug interactions with isobologram and the combination index values showed that sequential exposure to taxol followed by TNP-470 produced synergistic effects in these cell lines tested. Our findings suggest that such an angiocytotoxic chemotherapy might be promising for the treatment of NSCLC.
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PMID:Combined effects of TNP-470 and taxol in human non-small cell lung cancer cell lines. 961 59

The effects of lipoxygenase inhibitors were investigated using human lung cancer cell lines and A/J mice. By RT-PCR, 5-, 12-, and 15-lipoxygenase mRNA was detected in NSCLC cells. NDGA inhibited 5-LO activity in adenocarcinoma cell line NCI-H1264. Using an MTT assay, NDGA, MK591 and AA861 inhibited the growth of NSCLC cell lines tested with IC50 values of 3, 2, and 7 microM, respectively. Using a clonogenic assay, 10 microM NDGA significantly reduced NSCLC colony number. NDGA significantly slowed NSCLC xenograft growth in nude mice. When the tumors were excised and analyzed, nude mice treated with NDGA had significantly more apoptotic figures than did untreated tumors. A/J mice treated with urethane developed adenomas after 4 months and NDGA administration significantly reduced lung adenoma number. These data indicate that lipoxygenase inhibitors inhibit lung cancer growth and prevent lung carcinogenesis.
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PMID:Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth. 965 87

Many small cell lung tumors are dependent in vitro and in vivo on autocrine growth loops. The prototypical small cell lung cancer autocrine growth factor, gastrin-releasing peptide (GRP), is one of many peptide hormones which require post-translational carboxy-terminal alpha-amidation for bioactivity. We have reported that neuroendocrine human lung tumor cell lines express the bifunctional enzyme PAM which catalyzes the biosynthesis of alpha-amidated peptides in a two-step process, and have recently shown that non-small cell lung cancer cell lines and tumors, generally considered to be non-endocrine in nature, also express PAM. We have also shown that two chemical classes of PAM inhibitors, substrate analogues and specific copper chelators, inhibit amidating enzyme activity in cell-free extracts. Here we demonstrate in vitro growth inhibition of lung cancer tumor cell lines by both these classes of PAM inhibitors using the MTT assay and the clonogenic assay. Growth inhibition in a small cell lung cancer cell line can be overcome by exogenous addition of synthetic alpha-amidated GRP. Similar growth-suppressive effects are seen in cell lines stably transfected with a vector expressing antisense PAM RNA. These data support the mechanism of inhibition for a new type of chemotherapeutic/intervention agent, directed at synthesis and activation of peptide growth factors, and support our postulate that alpha-amidated peptide hormones are a common component in lung tumor autocrine growth biology which can be inhibited by targeting the biochemical mechanisms necessary for growth factor synthesis.
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PMID:Autocrine growth loops dependent on peptidyl alpha-amidating enzyme as targets for novel tumor cell growth inhibitors. 1041 97


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