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

Because of conflicting reports of clinical synergy, we used the tetrazolium-based colorimetric (MTT) assay to test in vitro combination effects of methotrexate (MTX) plus 5-fluorouracil (FUra) in 4 schedules on 2 human non-small-cell lung cancer cell lines (adenocarcinoma, NC1-H23; bronchio-alveolar-cell carcinoma, NC1-H358), and 1 human colorectal adenocarcinoma cell line (SNU-C1). The complete 3 dimensional set of isoboles in the dose range under study was generated by a microcomputer-based method. We found that the combination effects of 8-hr sequential FUra-MTX, simultaneous administration of MTX-FUra, and 8-hr sequential MTX-FUra were clearly antagonistic for all 3 cell lines. In contrast, the combination cytotoxic effects of 24-hr sequential MTX-FUra were much more active. Our in vitro model thus clearly shows that MTX-FUra interactions are highly schedule-dependent. This provides a rational basis for testing sequential MTX-FUra with a longer administration interval than usually employed clinically.
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PMID:Schedule-dependent in vitro combination effects of methotrexate and 5-fluorouracil in human tumor cell lines. 184 23

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

In vitro MTT assay was applied for examining chemosensitivity with 104 samples; 56 primary tumors, 31 lymph node, 9 liver, and 8 peritoneal metastases, obtained from 87 patients with advanced gastric carcinoma. The rate of effectiveness of various anticancer drugs were as follows; etoposide, 87.7%; cisplatin, 55.1%; mitomycin C, 51.5%; pirarubicin, 50.0%; aclarubicin, 48.8%; carboquone, 31.8%; doxorubicin, 20.3%; and 5-fluorouracil, 12.9%. Etoposide was found to be most effective against gastric carcinoma in this test. Concerning with the metastatic lesions, liver metastases were resistant to all tested drugs. On the other hand, peritoneal metastases were sensitive to etoposide, mitomycin C, and pirarubicin. The results indicate heterogeneity of the chemosensitivity between primary and metastatic lesions, and it was supposed that etoposide might be useful against human gastric cancer.
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PMID:[Chemosensitivity test for gastric cancer by in vitro MTT assay]. 190 13

We compared the in vitro sensitivity patterns to cytotoxic drugs and expression of the multidrug resistance-associated MDR1 gene (also known as PGY1 gene) in four gastric carcinoma cell lines with those obtained in a panel of 11 colorectal carcinoma cell lines. In addition, we tested the effects of leucovorin on enhancement of fluorinated pyrimidine-induced cytotoxicity. We used a semiautomated tetrazolium dye assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (tetrazolyl blue)] (MTT) to compare the drug sensitivity of the gastric carcinoma cell lines with that of the colorectal carcinoma cell lines. The gastric carcinoma cell lines were more sensitive to some drugs, including doxorubicin and cisplatin, but not to the fluorinated pyrimidines. Addition of leucovorin at a clinically achievable concentration enhanced the cytotoxic effects of both fluorouracil and floxuridine in colorectal carcinoma cell lines, but it enhanced the effects of only floxuridine in gastric carcinoma cell lines. With the use of a slot blot assay, relatively low levels of MDR1 RNA were present in all four gastric carcinoma cell lines, while intermediate or high levels were present in most of the colorectal carcinoma cell lines. In general, our findings reflect clinical experience and may help in the design of clinical trials.
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PMID:Chemosensitivity patterns and expression of human multidrug resistance-associated MDR1 gene by human gastric and colorectal carcinoma cell lines. 196 20

Beta-carotene and canthaxanthin at concentrations of 70 or 300 microM were shown to inhibit the proliferation of cultured human squamous cells (SK-MES lung carcinoma and SCC-25 oral carcinoma) in a 5 hr cell density assay. Responses were similar for both tumor cell lines, ranging from 71-84% inhibition. In contrast, equimolar concentrations of alpha-tocopherol gave only 19-36% inhibition of SCC-25, but 50-75% inhibition of SK-MES cell density. Equimolar reduced glutathione resulted in 4-15% stimulation of SCC-25 and 22-25% inhibition of SK-MES cell proliferation. With cultured normal keratinocytes, treated final cell densities did not differ significantly from those of controls. Two additional assays measuring the metabolic generation of formazan (MTT assay) and [5-3H]thymidine incorporation were in substantial agreement with the growth inhibition pattern. Thus both continuous and cyclic cellular processes are involved in the tumor-specific response. Onset of the response to beta-carotene alone or in combination with alpha-tocopherol is signalled within 1-2 hours of treatment by the appearance of a unique 70 kD heat-shock protein.
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PMID:Induction of a 70 kD protein associated with the selective cytotoxicity of beta-carotene in human epidermal carcinoma. 211 11

The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.
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PMID:Antitumor activity and pharmacokinetics of a morpholino-anthracycline derivative (KRN8602) against human breast carcinoma xenografts serially transplanted into nude mice. 214 15

Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM-CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin-stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml.
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PMID:A highly sensitive quantitative bioassay for human granulocyte-macrophage colony-stimulating factor. 220 65

A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay was developed and compared with 51Cr release from different adherent tumor cell targets (human squamous cell carcinoma lines of the head and neck established in our laboratory, melanoma, and colorectal carcinoma) using 5-7-day human lymphokine-activated killer cells and monocyte-depleted peripheral blood lymphocytes as effectors. With adherent tumor cell targets, MTT colorimetry was more sensitive than the 51Cr release assay in measuring the antitumor activity of effectors: median, 4385 (range, 988-8144) versus median, 1061 (range, 582-7294) lytic units (the number of effector cells required to lyse 20% of 5 x 10(3) targets)/10(7) effectors (P less than 0.01). Background effects (without effector cells) were comparable in 4-h assays (9% versus 10%) between MTT colorimetry and 51Cr release. In 24-h assays, MTT colorimetry showed higher antitumor activity (70-100% versus 40-60% lysis at 1:1 effector:target cell ratio) but lower background effects (6% versus 38%) than 51Cr release assay. Thus, MTT colorimetry was more sensitive, did not use radiolabeled targets, required fewer effector cells, and was easier, less expensive, and better adaptable to serial monitoring of effector cell function in cancer patients. This colorimetric assay is especially well suited to adherent tumor cell targets. The use of adherent tumor cell monolayers, as opposed to trypsinized single cell suspensions, provides an opportunity to measure interactions of effector cells with enzymatically unaltered solid tumor targets. Because of the greater sensitivity of the colorimetric assay, the transformation of MTT data into lytic units, as commonly used for 51Cr release assays, required an adjustment to avoid the extrapolation based on the exponential fit equation.
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PMID:Evaluation of tetrazolium-based semiautomatic colorimetric assay for measurement of human antitumor cytotoxicity. 234 May 18

Aliphatic triazenes, such as 1,3-dimethyltriazene, are potent biological alkylating agents because they form alkyldiazonium ions. They are also subject to very rapid proteolytic decomposition, even at physiological pH. The acylated analogues 1,3-dialkyl-3-acyltrizenes are much more stable in aqueous solution, but they also give rise to alkyldiazonium ions. Four acylated 1,3-dimethyltriazenes, where the acyl groups were diethylphosphoryl (DMP), carbethoxy (DMC), acetyl (DMA), and N-methylcarbamoyl (DMM), were studied kinetically. Rate-pH profiles indicated that the acyl group had a profound effect on the mechanism of decomposition. The cytotoxic potential of all four compounds was studied in vitro by using the MTT-tetrazolium assay. The compounds had fair-to-good activity against some cell lines, particularly those deficient in methylation repair. In vivo assays of DMC and DMM against several tumor xenografts in nude mice showed promising activity for some cancers, particularly in the case of DMM. In vitro assays were also carried out on three 1-(2-chloroethyl)-3-methyl-3-acyltriazenes. The acyl groups were carbethoxy (CMC), acetyl (CMA), and N-methylcarbamoyl (CMM). The activity of these compounds largely paralleled that of bis(2-chloroethyl)-N-nitrosourea (BCNU), except for those cell lines which exhibited the Rem phenotype; triazenes were more active in those lines than BCNU. The in vivo activity of CMC, CMA, and CMM was tested in the P388 leukemia assay. All three were active but CMC and CMA proved to be rather toxic. CMM was well tolerated and was examined in several tumor xenografts in nude mice. Significant activity was found against MX-1 mammary carcinoma, against LX-1 small cell lung carcinoma, and particularly against LOX amelanotic melanoma, where complete cures were effected. The antineoplastic activity of the acyltriazenes is well-correlated with their chemical behavior.
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PMID:1,3-Dialkyl-3-acyltriazenes, a novel class of antineoplastic alkylating agents. 239 96

We have routinely used a [3H]-uridine microplate assay for assessing chemosensitivity. A colorimetric assay with the advantages of safety, cost and simplicity has previously been described and relies on the ability of living cells to reduce a soluble tetrazolium salt, 3-4,5-dimethylthiazol-2,5-diphenyl-tetrazolium bromide (MMT), into an insoluble formazan precipitate. We compared the chemosensitivity of 14 human tumour cell lines of colonic, lung and cervical carcinoma origin to doxorubicin, vindesine or vindesine immunoconjugates in both the [3H]-uridine assay and a modified MTT assay to evaluate whether we could change to the non-radiolabelled method. Correlation between the concentration of drug causing 50% inhibition of cell growth (IC50) for these agents between the two assays was very poor. However, taking account of recent reports in the literature, we modified the MTT assay by removing serum-containing medium and using dimethyl sulphoxide to solubilise the formazan precipitate. This considerably improved the correlation between the assays for doxorubicin (r = 0.871; P = 0.001) and vindesine (r = 0.981; P less than 0.001). Our data indicates that the MTT assay can be used to replace the [3H]-uridine assay for chemosensitivity screening, but further modifications are necessary to improve the sensitivity and decrease the problem of cell loss after washing, which was noted with some adherent cell lines.
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PMID:Comparison of tetrazolium colorimetric and [3H]-uridine assays for in vitro chemosensitivity testing. 278 39


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