Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin (pirarubicin; THP) was assessed using human gastric cancer cell lines in vitro and in vivo. The cytotoxicity of THP on MKN-28 and MKN-45 was superior to that of adriamycin (ADM) as detected by a growth assay with an MTT colorimetric endpoint. When the same doses of THP and ADM were administered intraperitoneally to nude mice bearing St-15, St-40 and SC-1-NU, the antitumor activity of THP was almost equivalent to ADM in terms of relative mean tumor weight. However, the adverse effects of THP were also significantly lower than those of ADM in terms of death rate, body weight loss and spleen weight loss. This was also confirmed in THP or ADM combination chemotherapy with mitomycin C and 5-fluorouracil on St-15 and MKN-45. These results indicated that THP is a candidate anthracycline to replace ADM for combination cancer chemotherapy in gastric carcinoma.
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PMID:Antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin on human gastric cancer cell lines in vitro and in vivo. 801 50

5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis and phototoxicity in vitro was investigated in five malignant and two normal cell lines. Intracellular protoporphyrin IX (PpIX) content was quantified by extraction and fluorescence spectroscopy. Cellular PpIX content did not always correlate with cell proliferation rate as measured by the doubling times of cell lines. Cellular efflux of PpIX was also investigated. In a bladder carcinoma cell line, the observed rapid efflux was not blocked by verapamil, an inhibitor of the P-glycoprotein efflux pump. These data support the view that cellular PpIX accumulation is a dynamic process that is determined by both the efflux of PpIX from the cells and enzyme activities in the haem biosynthesis pathway. Desferrioxamine (desferal), a modulator of PpIX biosynthesis, enhanced ALA-induced cellular PpIX content significantly in all carcinoma cell lines but not in non-malignant cell lines. The enhanced PpIX cellular accumulation is attributed to inhibition of ferrochelatase activity, the enzyme responsible for the conversion of PpIX to haem. PpIX-mediated cellular photodestruction following irradiation with an argon ion laser at 514.5 nm was determined by the 'MTT assay'. There appeared to be a 'threshold' effect of cellular PpIX content; cells that synthesised less than 140 ng/mg-1 protein exhibited very little phototoxic damage, while cell lines having greater than 140 ng PpIX/mg-1 protein [corrected] exhibited a consistent phototoxic response. Among the cell lines which did undergo phototoxic damage, there was not a strict correlation between PpIX cellular content and ALA-induced phototoxicity. Desferal enhanced the PpIX content and phototoxic effect in the responsive cells. Fluorescence microscopy of the ALA-treated cells revealed marked accumulation of PpIX in mitochondria (rhodamine 123 co-staining). That the primary site of phototoxic damage is also the mitochondria was confirmed by electron micrographs of cells photosensitised with ALA-induced PpIX, which showed swelling of mitochondria within minutes after irradiation while other suborganelles appeared to be unaffected. The repair or further destruction of the mitochondria was fluence and cell-type dependent. The data from this study suggest that the basis of increased ALA-induced PpIX accumulation in tumours is a combination of various aspects of the metabolic process and pharmacokinetics and that the efficacy of photodestruction of malignancy will be determined not only by the rate of PpIX synthesis but also by specific cellular and tissue characteristics.
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PMID:A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin. 801 36

Insulin-like growth factors (IGFs) are potent proliferation stimulators for numerous tumor cells and often function as autocrine growth factors. We have previously shown that exogenous IGF-I and IGF-II enhance proliferation of colorectal carcinoma cells. The biological signal of both factors is transmitted through the IGF-I receptor (IGF-I-R). This receptor was expressed in 12/12 colorectal carcinoma cell lines tested. alpha IR3, a neutralizing monoclonal antibody (MAb) directed against the human IGF-I-R, inhibited proliferation in 7/12 lines (Caco-2, HT-29, LS411N, LS513, LS1034, WiDr and SW620), as reflected by a reduction of MTT conversion (19 to 42%), a decrease in cell number (39 to 72%) and an increase in doubling time (up to 2-fold). In addition, in 4 cell lines (Caco-2, LS513, LS1034, WiDr) alpha IR3 suppressed colony formation in methylcellulose (40 to 84%). Excess of exogenous IGF completely neutralized alpha IR3-mediated inhibitory effects. Northern blot analysis revealed abundant expression of 2 IGF-II transcripts of 5.0 and 4.3 kb in LS1034 cells. In addition, we observed that growth inhibition by alpha IR3 was correlated with a more differentiated phenotype. Our results suggest that growth of many colorectal carcinoma cell lines is regulated by autocrine IGF-II-mediated stimulation of the IGF-I-R.
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PMID:Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop. 805 Aug 27

The search for improved photosensitizers for laser phototherapy of malignancies has led to the examination of a new group of carbocyanine dyes as effective fluorochromes. In this study, four carbocyanine dyes with different absorption maxima of 483 nm [DiOC6(3)], 545.5 nm (DiIC5(3)], 556.6 nm [DiSC5(3)], and 651.0 nm [DiSC3(5)] were tested in vitro. The kinetics of uptake and toxicity of these four dyes were assessed for P3 human squamous cell carcinoma, HT29 colon carcinoma, M26 melanoma, and TE671 fibrosarcoma cell lines at 15, 30, 45, 60, and 180 minutes after exposure with each dye. After sensitization with DiOC6(3), the P3 and M26 cell lines were also tested for phototherapy by treatment with 488-nm light from an argon laser. The results showed that these four carbocyanine dyes had rapid and significant uptake by the carcinoma cell lines with no toxicity at concentrations < 0.1 micrograms/mL. Nontoxic DiOC6(3) levels in sensitized tumor cells after laser phototherapy resulted in approximately 85% inhibition of P3 and approximately 95% inhibition of M26 cell lines by MTT assays. The results suggest that these carbocyanine dyes can be used for tumor photosensitization and wavelength-matched laser photodynamic therapy. Further in vivo studies will be necessary to define the clinical potential of carbocyanine dyes as tumor-targeting agents for phototherapy of cancer.
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PMID:Evaluation of four new carbocyanine dyes for photodynamic therapy with lasers. 805 86

The MTT assay in agarose, a simple colorimetric test performed in double-layer agarose, has been evaluated for chemosensitivity testing of fresh tumor samples from human cancers in comparison with the MTT assay. The absorbance of cells from fibroblast cell lines or normal tissues was markedly reduced in agarose. The chemosensitivity of cells from a carcinoma cell line or fresh tumor tissues was not apparently affected by the presence of almost 50% of fibroblast or nonmalignant cells in the MTT assay in agarose, whereas it did so in the MTT assay. The frequency of the differences between chemosensitivity of fresh tumor samples in both assays was increased, when the tumor tissue cells contained a higher proportion of nonmalignant cells, i.e. vimentin-positive cells. In 173 patients with various carcinomas, in vitro sensitivity to 7 drugs in the MTT assay in agarose was significantly greater than that in the MTT assay. Further, the MTT assay in agarose had a higher accuracy for prediction of either sensitivity or resistance than the MTT assay in a total of 38 in vitro-in vivo correlations. These results indicated that the MTT assay in agarose was a more suitable technique for the application to chemosensitivity of fresh tumor samples from patients with various carcinomas as compared to the MTT assay.
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PMID:Evaluation of MTT assay in agarose for chemosensitivity testing of human cancers: comparison with MTT assay. 805 82

Simvastatin (SV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits the synthesis of mevalonic acid. The dose-dependent (0.1-100 micrograms/ml) cytotoxicity of SV towards human (MIAPaCa-2, Panc-1, HPC-1, HPC-3, HPC-4, PK-1, PK-9) and hamster (T2) pancreatic carcinoma cell lines was determined by MTT assay. At up to 20 micrograms/ml of SV, the effect was reversible and was restored by 60 micrograms/ml mevalonic acid. Point mutation of Ki-ras at codon 12 in each cell line was detected by means of the modified polymerase chain reaction. The concentration of SV necessary to achieve 50% cytotoxicity was about 10 micrograms/ml, and at this concentration of SV, DNA synthesis assayed in terms of [3H]thymidine uptake, isoprenylation of p21ras examined by Western blotting and cell progression from G1 to S phase of the cell cycle analyzed by flow cytometry were all inhibited. Isoprenylation inhibitors of p21ras, such as SV, are expected to be useful for the treatment of pancreatic cancer.
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PMID:Cytotoxicity of simvastatin to pancreatic adenocarcinoma cells containing mutant ras gene. 806 17

We previously found that human cervix carcinoma HeLa cells irradiated with multiple fractions of gamma rays (0.5 Gy daily, five times per week over 6 weeks) become resistant to cis-dichlorodiammineplatinum(II) (cis-DDP), methotrexate (MTX) and vincristine (VCR), but retain the same sensitivity to gamma rays or UV light. In the present report attempts were made to elucidate the mechanisms by which these cells have acquired resistance to cis-DDP and VCR. The sensitivity to different drugs was measured by modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Neither buthionine sulfoximine (BSO) nor ethacrinic acid were able to reverse the resistance of preirradiated cells to cis-DDP. Therefore, neither the increased levels of glutathione nor glutathione transferase seem to be involved in resistance to cis-DDP. Preirradiated cells did show resistance to cadmium, indicating the increased levels of metallothioneins in these cells. Resistance of preirradiated cells to vincristine was abolished by the addition of verapamil, indicating that resistance to this drug may depend on the increased expression of plasma membrane P-glycoprotein. It was concluded that mechanisms of resistance of preirradiated cells to cytostatics are multifactorial and involve at least the increased levels of metallothioneins and changes in the plasma membrane. Acquired resistance to cytotoxic drugs induced by preirradiation may be the reason for the reduced response to these drugs after radiation treatment of certain tumors.
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PMID:Multifactorial molecular mechanisms are involved in resistance of preirradiated human cervix carcinoma cells to cis-dichlorodiammineplatinum (II) and vincristine. 810 78

Human cervical carcinoma HeLa cells were made resistant to cisplatin by one of two schedules; "acute" (cells repeatedly treated with cisplatin for 1 h in serum-free medium--CA cells) or "continuous" (cells treated repeatedly for 24 h in complete medium--CK cells). The sensitivity of CA and CK sublines to cisplatin and various other antineoplastic drugs was determined by the modified MTT staining procedure. The possible involvement of glutathione (GSH), glutathione S-transferases (GST) and metallothioneins (MT) in cisplatin resistance was examined. The results show that acutely treated CA cells became more resistant to cisplatin than CK cells. The resistance to cisplatin does not involve either glutathione or glutathione transferase. The increased levels of metallothioneins might be involved in the development of resistance. The sensitivity of CA and CK sublines to the selected drugs was different from that of the parent cells. Both sublines became cross-resistant to vincristine and methotrexate, but only CA cells exhibited cross resistance to etoposide doxorubicin and 5-fluorouracil. Thus, the development of resistance to cisplatin is a consequence of numerous intracellular alterations that are reflected in cell response to a variety of anticancer drugs. The response depends on the schedule of resistance development and on the nature of the secondary agent.
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PMID:The characterization of two human cervical carcinoma HeLa sublines resistant to cisplatin. 812 44

The objective of the present in vitro study was to determine an optimal timing of the irradiation in the combination cisplatin (CDDP) and 5-fluorouracil-folinic-acid (5-FU-FA) allowing a maximal cytotoxic effect on a human cell line derived from a head and neck carcinoma (CAL 27 cells). The various tested chemoradiotherapy sequences were applied in parallel to human keratinocytes in culture (SVK 14 cells). This was done in order to define the best sequence allowing the achievement of an optimal selectivity of the cytotoxic effects. The drug sequence was: CDDP over 2 h then fresh medium was added including the tandem 5-FU-d,I FA applied 6 h after CDDP, for 5 days. Irradiation was applied only once and at various times within the drug sequence. The cytotoxicity effects of the different chemoradiotherapy combinations were assessed by the MTT semi-automated test. The part taken by the 5-FU-FA combinations in the overall cytotoxicity was examined; an effect was apparent on CAL 27 cells only. The evolution of the radiation effect (RE = cell survival after drugs/cell survival after drugs plus irradiation) was analysed as a function of the different times of irradiation within the given drug sequence. Clearly, the RE values were dependent upon time at which the radiation dose in the chemoradiotherapy regimen was administered. For CAL 27 cells, irradiation effects were maximal at the first irradiation time tested after the end of the CDDP exposure (i.e. t = 3.5 h). In contrast, this optimal chemoradiotherapy timing for better cytotoxicity on CAL 27 cells did not correspond to that of SVK 14 cells. Consequently, it was possible to establish that the best time for the selectivity index was located shortly after the CDDP exposure.
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PMID:Importance of the irradiation timing within a chemoradiotherapy sequence including cisplatin and 5-FU-folinic acid. Experimental results. 821 57

The present study was designed to analyze the growth-inhibitory effects of the combination of fluorouracil (FUra), cisplatin (CDDP), and dipyridamole (DP). These toxic effects were assessed on the human breast-carcinoma cell line MCF-7 using the MTT (tetrazolium bromide) assay in 96-well culture dishes. Data were analyzed using the median-effect principle. The drug combinations tested included FUra concentrations ranging from 0.8 to 800 nmol/l, CDDP concentrations of 0.3-30 mumol/l, and DP concentrations of 2-200 mumol/l. A total of 189 different experimental conditions were tested, including different sequences of administration, with being DP applied before, simultaneously with, or after the two antitumor drugs. Synergistic cytotoxic interactions were found between FUra and CDDP, FUra and DP, and CDDP and DP as well as when the three drugs were combined. The sequence of exposure did not influence the growth-inhibitory activity of the combination FUra-CDDP but altered the effect of combinations of either FUra or CDDP with DP, since at lower concentrations the effect shifted from synergism to antagonism when DP was added simultaneously with CDDP and after the two antitumor drugs. However, the interaction was shown to be truly synergistic by median-effect analysis when the two antitumor drugs were simultaneously associated, with no change in the synergistic effect being observed for the three DP administration sequences.
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PMID:Sequence-dependent growth-inhibitory effects of the in vitro combination of fluorouracil, cisplatin, and dipyridamole. 826 77


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