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

MTT staining procedures have been used in chemosensitivity testing of established cell lines of human and other sources as well as of human leukaemias, but only limited information on its application in primary solid human tumors is presently available. We have evaluated MTT staining in primary human Renal Cell Carcinomas (RCCs), studied various factors interfering with the optimal use, and finally applied it in subsequent chemosensitivity testing. The method depends on the conversion of a water-soluble tetrazolium salt (MTT) to a purple colored formazan precipitate, a reaction effected by enzymes active only in living cells. Single cell suspensions of RCCs were obtained either by enzymatic dispersion or by mechanical dissagregation, filtered through gauze, and purified by Ficoll density centrifugation. Tests were carried out in 96-well microculture plates. 10(4) viable tumor cells per well at 4 h incubation time with 20 micrograms MTT/100 microliters total medium volume yielded best results. Formazan crystals were dissolved with DMSO, and the plates were immediately measured on a microculture plate reader at 540 nm. Under these criteria, linearity of the system could be demonstrated. For chemosensitivity testing, cells were continuously exposed to a number of drugs prior to the MTT staining procedure. Reproducibility of results was assessed and confirmed by culturing RCCs in flasks additionally, resubmitting them after 1, 2, and 4 weeks to the MTT assay. We conclude that the semiautomated MTT assay offers a valid, rapid, reliable and simple method to determine the degree of chemoresistance in primary human RCCs.
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PMID:Chemosensitivity testing of primary human renal cell carcinoma by a tetrazolium based microculture assay (MTT). 169 48

In this study, we compared the cytotoxicity of cisplatin and carboplatin against a panel of human ovarian cancer cell lines using the MTT assay, a rapid colorimetric test that can be used to evaluate the number of residual viable tumor cells following chemotherapy. The established human ovarian cancer cell line OVCAR-3 and the recently isolated and characterized A721, A90, A286, A1, and A121A cell lines were evaluated for chemosensitivity. Each cell line was treated separately with cisplatin and carboplatin at concentrations ranging from 500 to 0.16 micrograms/ml. Various chemotherapeutic exposure periods (1, 4, 24, and 48 hr) were tested to determine maximal efficacy. All cell lines were more susceptible to cisplatin than carboplatin at all drug concentrations and all exposure periods tested (P = 0.005). The overall median 50% inhibitory concentration (ID50) for cisplatin was 107 micrograms/ml compared with 490 micrograms/ml for carboplatin P = 0.005). For both cisplatin and carboplatin a 24-hr exposure was significantly more cytotoxic than a 1-hr exposure (P = 0.003 and P = 0.006, respectively). These in vitro results suggest that cisplatin is significantly more cytotoxic than carboplatin against human ovarian cancer cell lines and that cisplatin should not be replaced by carboplatin in the treatment of advanced epithelial ovarian cancer until randomized trials using maximum dosing of the cisplatin-containing regimen are performed.
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PMID:Comparison of cisplatin and carboplatin cytotoxicity in human ovarian cancer cell lines using the MTT assay. 169 53

Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood, but in recent years a number of IFN-inducible genes, the presumed mediators of IFN action, have been identified. In the present study we examined the antiproliferative effect of IFN-alpha and IFN-gamma on human breast cancer cells (MCF-7) using (i) the MTT dye formation assay and (ii) anchorage-independent (AI) growth in soft agar. Both IFN-alpha and IFN-gamma were found to have an antiproliferative effect on the growth of MCF-7 cells. In addition, the kinetics of induction of a number of IFN-inducible genes was also examined. The expression of these genes was measured by mRNA analyses using specific [alpha-32P]-labeled cDNAs as probes. The induction of these genes by IFN-alpha and IFN-gamma is a primary effect of IFN, as de novo protein synthesis is not required for their induction. Our results on the kinetics of induction of these genes by IFN-alpha and IFN-gamma suggests a complex mechanism of ligand-dependent gene activation in this cell line with some similar and dissimilar pathways.
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PMID:Interferon-alpha and gamma mediated gene responses in a human breast carcinoma cell line. 171 85

beta-Sitosterol (SI-0), beta-sitosterol glucoside (SI-1), dioscin (SI-2), methyl protoprosapogenin A of dioscin (SI-3), methyl protodioscin (SI-4) and protodioscin (SI-5) were isolated and characterized from the whole plant of Solanum indicum L. (Solanaceae). Except for beta-sitosterol, these compounds have not been previously isolated from Solanum indicum L. Both CHCl3 soluble (SI-IV) and insoluble (SI-V) fractions of the ethanolic extract (SI-I) showed cytotoxicity on seven cancer cell lines: Colo-205 (colon), KB (nasopharynx), HeLa (uterine cervix), HA22T (hepatoma), Hep-2 (laryngeal epidermoid), GBM8401/TSGH (glioma) and H1477 (melanoma). The purified constituents, SI-2 and SI-4 showed more potent effects by DEA and MTT assay. SI-2,3,4 and 5 also demonstrated cytotoxicity on cultured C6 glioma cells by PRE assay, ans SI-3,4 and 5 showed a tumor inhibitory effect in vivo in C6 glioma cells. In addition, SI-2 had an inhibitory effect on the DNA synthesis of C6 glioma cells at 10 micrograms/ml.
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PMID:Experimental antitumor agents from Solanum indicum L. 176 63

Utility of drug response modulators to increase therapeutic:toxic ratio of anticancer drugs in the treatment of refractory malignancies is becoming desirable. In this study, we have attempted to potentiate the tumor cell killing ability of Adriamycin (ADR) against chronic myeloid leukemia cells (CML), in the presence of vitamin K3. Cell growth was evaluated by the MTT assay and the 3H-thymidine incorporation inhibition assay. A highly significant (p less than 0.001) inhibition of cell survival and 3H-thymidine incorporation was effected in CML cells exposed to the combination of ADR and vitamin K3. When the CML cells were treated with ADR and vitamin K3 simultaneously, a greater fragmentation of the intact DNA was revealed as observed by the enhanced formation of DNA single strand breaks. Results demonstrate the therapeutic significance of employing vitamin K3 as an adjuvant in CML chemotherapy with ADR.
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PMID:Single and combination treatment with vitamin K3 and adriamycin: in vitro effects on cell survival and DNA damage in human chronic myeloid leukemia cells. 177 Dec 99

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

Vitamin K3 was employed as a resistance-modifying agent to investigate its activity in enhancing mitoxantrone (MITO)-induced cytotoxicity in parental (P388/S) and multidrug resistant (P388/ADR) P388 leukemia cells. Vitamin K3 potentiated the antitumor effects of MITO in P388/S and P388/ADR tumor cells as monitored by inhibition of tumor cell survival (MTT assay). MITO and vitamin K3 in combination effected an enhanced inhibition of [3H]thymidine (DNA synthesis) and [3H]uridine (RNA synthesis) and also increased the life span of the sensitive and resistant tumor-bearing animals. The effect of vitamin K3 on the induction of DNA strand breaks by MITO was also examined. Increased fragmentation of DNA was illustrated in the sensitive and resistant P388 leukemia cells exposed to the combination. Observations indicate the restoration of sensitivity in P388/ADR cells to MITO by vitamin K3 that may be due to its ability to increase the MITO-induced DNA strand breaks.
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PMID:Antiproliferative effects of mitoxantrone in ADR-sensitive and ADR-resistant P388 leukemia cells enhanced by vitamin K3. 180 14

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

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

Antitumor activity of the thermosensitive liposome, TAC-1043, was examined. The TAC-1043, produced by Takeda Chemical Industries, Ltd., contained entrapped cisplatin in a large unilamellar vesicle (LUV). LUV is composed of dipalmitoylphosphatidyl choline (DPPC) and distearoylphosphatidyl choline (DSPC) in the ratio of 9:1. The in vitro sensitivity of TAC-1043 was examined by SDI assay with MTT, using human esophageal cancer cell lines (TE-2, KY). TAC-1043 was effective at the concentration of 10 micrograms/ml, 41 degrees C and 43 degrees C. The in vivo effect of TAC-1043 together with hyperthermia was examined using mouse tumor MM 48. TAC-1043 combined with hyperthermia significantly suppressed the tumor proliferation.
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PMID:[Hyper-thermo chemotherapy of esophageal cancer with thermosensitive liposome, TAC-1043]. 187 16


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