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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe our experience with succinic dehydrogenase inhibition (SDI) test for solid tumors as a chemosensitivity test using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Specimens were obtained from 76 surgical resected tumors, including 32 colon cancers, 24 stomach cancers and 16 lung cancers. Following enzymatic dissociation of scissors-minced tumors, viable cells were cultured in serum free medium (S-Clone SF-B) for 4 days with eight drug concentrations obtained by 2-fold dilution of drugs. Among 76 specimens tested, 48 specimens including 15 colon cancers, 18 stomach cancers and 15 lung cancers were successfully evaluated. For the purpose of judgement, 50% inhibitory concentration (IC50) was calculated in each case. Tumor specimen was regarded as sensitive to a given agent when the IC50 value was the same or smaller than the cut-off concentrations (1 microgram/ml for mitomycin C, 5 micrograms/ml for cisplatin, 2 micrograms/ml for adriamycin and 50 micrograms/ml for 5-fluorouracil), and was regarded as resistant when it was larger than these levels. In vitro vs in vivo drug sensitivity was successfully evaluated in 23 cases. The overall predicting accuracy rate was 78% (18/23), with one true positive, 5 false positive and 17 true negative cases. This test appeared to be useful to tailor effective agents for patients because of its relatively high successful and predictive rates.
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PMID:[Comparison between clinical response and in vitro chemosensitivity of solid tumors in the succinic dehydrogenase inhibition test]. 172 63

Menadione (vitamin K3, 2-methyl-1,4-naphthoquinone) is a synthetic derivative of napthoquinone. Its ability to inhibit cell growth in a wide variety of and human tumor cell types, and in rat hepatocytes has been recognized. Using a rat transplantable hepatoma model, we have evaluated the cytotoxic activity of menadione in hepatoma cells. Tumor cells in culture were sensitive to menadione treatment. The ID50 of drug is 3.4 microM as shown by a colorimetric MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Tumor-bearing rats were randomized into the treatment (n = 16) and control (n = 15) groups. Rats in the treatment group received intraperitoneal injection of menadione (10 mg/2 ml) once a week for four times; the control group received 2 ml water instead. None of the control rats survived after the 17th day following the start of treatment, while 5 out of the 16 treated rats responded well and survived long-term (greater than 60 days). Medadione was shown to inhibit actively the growth of hepatoma cells in vitro as well as in vivo.
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PMID:The in vitro and in vivo cytotoxicity of menadione (vitamin K3) against rat transplantable hepatoma induced by 3'-methyl-4-dimethyl-aminoazobenzene. 177 38

To investigate the possibility that anticancer drugs combined with cytokines may show increased activity, human tumor cells were treated with combinations of human recombinant interleukin 1 alpha (rIL-1 alpha) and etoposide (VP-16). The cytotoxicity of these combinations was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay using rIL-1 alpha-sensitive A375-C6 melanoma cells and A375-C5 cells, a clonal variant line that is resistant to IL-1 alpha. Data were analyzed for synergism by the median effect principle of T-C. Chou and P. Talalay (J. Biol. Chem., 252: 6438-6442, 1977). At a dose ratio of VP-16 to rIL-1 alpha of 12 nM:1 unit/ml in either simultaneous or sequential exposure (VP-16 first), the calculated combination index values indicated synergistic cytotoxicity toward both A375-C6 cells and A375-C5 cells. IL-1 alpha treatment 24 h prior to VP-16 exposure had no advantage over simultaneous treatment. Surface IL-1 alpha receptors on both A375-C6 and A375-C5 cells were measured using 125I-radiolabeled rIL-1 alpha binding; A375-C6 cells had 701 +/- 128 (SD) receptor molecules/cell and A375-C5 cells only had 58 +/- 33 receptor molecules/cell. The dissociation constants for IL-1 alpha were similar in both cell types (19 +/- 6 pM for A375-C6 and 17 +/- 2 pM for A375-C5). The specific binding of rIL-1 alpha to the surface IL-1 alpha receptors of both sensitive and resistant cells was significantly increased in a dose-dependent fashion by the prior treatment with VP-16 (1.75-fold on A375-C6 cells and 3.5-fold on A375-C5 cells). VP-16 also enhanced the internalization of receptor-bound rIL-1 alpha, suggesting that a possible mechanism of the synergistic cytotoxicity of rIL-1 alpha and VP-16 might be related to the modulation of rIL-1 alpha receptors by VP-16, resulting in increased internalization of rIL-1 alpha.
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PMID:A role for the interleukin 1 receptor in the synergistic antitumor effects of human interleukin 1 alpha and etoposide against human melanoma cells. 182 25

Primary cultured rat epidermal keratinocytes were used as an experimental model to detect oxidant-mediated adverse effects of dithranol (anthralin), a widely used antipsoriasis drug with tumor-promoting and skin-irritating properties. Keratinocytes were isolated and prepared from the skin of neonatal rats by a trypsin flotation method. Highly proliferative monolayer cells cultured in a serum-free medium were exposed to the test compound at concentrations (5-100 microM) used therapeutically for the treatment of skin disorders. Cytotoxicity was evaluated by changes in plasma membrane integrity (lactate dehydrogenase leakage), lysosomal function (neutral red uptake), and mitochondrial metabolic activity (reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, MTT). Exposure of keratinocytes to dithranol produced time- and concentration-related toxic responses. MTT reduction was found to be a more sensitive endpoint of cytotoxicity, showing significant toxic effects at 2 hr, while significant leakage of lactate dehydrogenase did not result until 6 hr. Oxygen consumption in keratinocytes and isolated mitochondria showed a similar pattern after exposure to dithranol. Increased cyanide-insensitive respiration was also noted. Oxidative stress, measured by superoxide anion-dependent reduction of nitroblue tetrazolium, occurred before dithranol produced cytotoxicity in the keratinocyte cultures. Superoxide formation, which increased with time after dithranol exposure, was detected both extracellularly and intracellularly and was inhibited by the addition of superoxide dismutase. Dithranol-induced cell injury was partially prevented by treatment with superoxide dismutase, and greater protection was shown by concurrent treatment with superoxide dismutase plus catalase. These findings suggest that the superoxide anion and hydrogen peroxide may be involved in the cytotoxicity of dithranol and that a culture system of rat keratinocytes may be useful in evaluating the mechanism of toxicity of dermatotoxicants.
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PMID:Dithranol-induced cytotoxicity in primary cultures of rat epidermal keratinocytes. I. The role of reactive oxygen species. 184 45

Topsentin, a bis(indolyl)imidazole marine natural product, inhibited the proliferation of cultured human and murine tumor cells at micromolar concentrations (IC50 values ranged from 4 to 40 microM) and was active against in vivo P388 leukemia (%T/C = 137, 150 mg/kg, QD1-5) and B16 melanoma (%T/C = 144, 37.5 mg/kg, QD1-9) tumors. Effects of 30 microM topsentin (1-hr exposures) on incorporation of radiolabeled precursors by P388 cells indicated inhibition of DNA synthesis (91%) and to a lesser extent RNA synthesis (57%), whereas synthesis of protein was unaffected (0%). Fluorescence spectral changes and competitive binding experiments with ethidium bromide indicated that topsentin interacted with DNA. No evidence for intercalation was observed in DNA unwinding studies, but competitive binding experiments with Hoechst 33342 and CC-1065 indicated that topsentin bound to DNA in the minor groove.
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PMID:Antitumor activity and biochemical effects of topsentin. 186 31

A new tetrazolium analog of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was evaluated as a substitute for MTT in the microculture screening assay for in vitro cell growth. This new tetrazolium compound, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS), in the presence of phenazine methosulfate (PMS), gave a water-soluble formazan product that had an absorbance maximum at 490-500 nm in phosphate-buffered saline. The amount of colored product formed was proportional to the number of cells and the time of incubation of the cells with MTS/PMS. MTS/PMS was reactive in all the cell lines tested which included mouse leukemia L1210 cells, mouse Ehrlich tumor cells, mouse 3T3 fibroblasts, and human colon tumor cells (HT-29). HT-29 and 3T3 fibroblasts reduced MTS/PMS more efficiently than they reduced MTT. Comparable to the amount of product formed from MTT, MTS/PMS gave excellent product formation. The IC50 value for pyrazoloimidazole obtained using MTS/PMS was 200 microM; for 5-fluoro-2'-deoxyuridine, the IC50 value was 0.9 nM. These values compared very favorably with the IC50 values obtained by direct cell counts. Further, the same IC50 values were obtained when the absorbances of the formazan product in the 96-well plates were determined after different times of incubation.
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PMID:Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. 186 54

A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly.
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PMID:Antiproliferative effects of cytokines on squamous cell carcinoma. 190 Jan 61

To clarify the influence of stromal cells on the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assay (MTT assay), a gastric carcinoma cell line (KATO-III) and a human fibroblast cell line (IMR-90) were subjected to a colorimetric assay, in which the chemosensitivity KATO-III was found to be highly sensitive to mitomycin C at 10 micrograms/ml, whereas IMR-90 was insensitive to mitomycin C at the same concentration. When the mixtures of these two cell lines were tested by the assay, a mixture of more than 25 per cent stromal cells reduced the sensitivity of KATO-III to mitomycin C. This suggested that the stromal cells in fresh surgical specimens might reduce the apparent sensitivity of the tumor cells.
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PMID:The influence of stromal cells on the MTT assay (I)--In vitro chemosensitivity of the tumor and stromal cells to mitomycin C. 190 57

A fresh surgical specimen from colon carcinoma was tested by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assay (MTT assay) and transplanted into nude mice. After 5 transfers in male BALB/c nude mice, the xenograft was then tested again by the MTT assay. It was found that the in vivo chemosensitivity pattern of the xenograft was essentially identical to that of the in vitro fresh surgical specimen, whereas the sensitivity of the xenograft was increased. To exclude the stromal cells from the nude mouse, anti-BALB/c serum was added to the primarily cultured colon carcinoma xenograft, and its chemosensitivity to mitomycin C (MMC) assessed. Although the sensitivity of the serum-treated group to MMC was slightly higher than that of the untreated group, the dose-response curves of the tumor cells to MMC were similar to each other. Thus, the chemosensitivity pattern of tumor cells seemed to be stable with or without normal cells, although the sensitivity itself was reduced by the presence of normal cells.
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PMID:The influence of stromal cells on the MTT assay (II)--Study on the nude mouse system. 190 58

We demonstrate that PCR amplification of human genomic DNA can be used for the detection of loss of heterozygosity (LOH) in tumor samples. A 250-bp fragment containing codon 72 of the human p53 gene was amplified, ThaI digested and electrophoresed. Tumor LOH is detectable both by ethidium bromide staining and autoradiography, despite 25% contamination with normal DNA. This technique provides a fast and reproducible alternative to conventional Southern blotting and has minimal sample requirements.
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PMID:Detection of loss of heterozygosity in tumor DNA samples by PCR. 193 Oct 11


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