Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Jpn J Cancer Res 1990 Aug
PMID:Antitumor activity and pharmacokinetics of a morpholino-anthracycline derivative (KRN8602) against human breast carcinoma xenografts serially transplanted into nude mice. 214 15

For chemosensitivity testing, a rapid in vitro colorimetric method (MTT assay) was used. Eleven head and neck cancer cell lines were investigated to distinguish five known active agents from five compounds inactive in phase II studies. Evaluation of the reliability of the assay for assessing drug sensitivity in this tumor cell population was done by correlating the in vitro results with reported in vivo response data. Methotrexate and cisplatin (clinically active) and vindesine and doxorubicin (less active clinically) were recognized in vitro as active and correlated well with clinical experience. Bleomycin (clinically active) was ineffective against some cell lines. The in vitro findings for the clinically inactive drugs (deoxyazacytidine, lomustine, and carmustine) also corresponded. Amsacrine and etoposide, contrary to clinical experience, showed activity in vitro. Further comparison of MTT assay results with clinical data is warranted and essential before its use in large-scale drug screening studies.
Eur J Cancer 1990
PMID:Validation of clinical predictive value of in vitro colorimetric chemosensitivity assay in head and neck cancer. 214 7

Twenty-five cell lines derived from nine different human cancers were tested for the cytotoxic activity of suramin. Two different initial cellular concentrations were used: C1 (800-2000 cells per well) and C2 (3000-7000 cells per well). Suramin concentrations ranged from 50 to 2500 micrograms/ml. Cytotoxicity was assessed by the MTT test. Epidermal growth factor receptors (EGFR) were assayed by competition analysis and Scatchard plots. In sixteen cell lines suramin had an unexpected growth stimulation effect at low concentration (50-125 micrograms/ml). IC50 varied from 21 micrograms/ml (osteosarcoma, OS2) to 1408 micrograms/ml (melanoma, CAL 24) and, within melanoma cell lines, it varied from 120 micrograms/ml (CAL 41) to 1408 micrograms/ml (CAL 24). The individual IC50 values were positively and significantly linked with the initial cellular density. Eighteen cell lines had measurable EGFR (six with two families of sites, twelve with one): Kd varied between 0.004 nmol/l for the highest affinity site (melanoma, CAL 7) to 1.852 nmol/l for the lowest affinity site (lung, CAL 12). There was no relation between presence or absence of EGF binding sites and distribution of IC50, but for cells with measurable EGFR there was a weak but significant correlation between the number of EGF binding sites per cell and the corresponding IC50 (r = -0.53, P = 0.021).
Eur J Cancer 1990
PMID:Epidermal growth factor receptor expression and suramin cytotoxicity in vitro. 214 26

Reduced folates have been shown to increase the cytotoxicity of 5-fluorouracil (FUra) by stabilizing the fluorodeoxyuridine monophosphate:thymidylate synthase complex, thus increasing the block in the DNA synthetic pathway. Using an in vitro tetrazolium colorimetric (MTT) cytotoxic assay, we tested the effects of FUra and 5-fluorodeoxyuridine (FUdR) with and without leucovorin (LV) on a panel of 7 human lung cancer cell lines. LV at a concentration of 20 microM enhanced the cytotoxicity of FUra and of FUdR in all of the cell lines. Quantitatively, LV had a higher degree of enhancement on FUdR than on FUra cytotoxicity in 6 cell lines. There was equivalent enhancement in the only remaining line. The differential effects of LV on the cytotoxicity of FUra vs. FUdR in these lung carcinoma lines contrasts with a quantitatively similar enhancement of cytotoxicity between FUra and FUdR in colon cancer lines previously reported from our laboratory. This suggests that the metabolism of FUra may be different in these lung cancer cell lines.
Int J Cancer 1990 Jul 15
PMID:Enhancement of fluorinated pyrimidine-induced cytotoxicity by leucovorin in human lung cancer cell lines. 216 87

Tumor necrosis factor alpha (TNF) exhibits cytotoxic activity on some solid tumors and has been reported to be synergistic with topoisomerase-II-targeted antineoplastic agents. A wide range of TNF concentrations (from 10 to 10,000 U/ml) was tested in 9 human lung cancer cell lines (5 small-cell and 4 non-small-cell carcinomas) using a semi-automated MTT assay. TNF was not cytotoxic in 8 cell lines, while an adenocarcinoma cell line was marginally sensitive to the cytokine. Using 125I-TNF we were able to show the presence of specific binding sites for TNF in 4/9 human lung cancer cell lines. Scatchard analysis of the marginally sensitive cell line showed high-affinity, saturable binding. With 5 cell lines we also tested whether TNF affected the cytotoxicity of doxorubicin and etoposide, 2 topoisomerase II-targeted drugs which are widely used in the therapy of lung cancer. No significant increase in cytotoxicity was seen when TNF was added to the 2 anti-neoplastic agents. In contrast to certain other human and mouse lines, human lung cancer cell lines appear to be resistant to TNF, despite the presence of the receptor in some of them; moreover, no synergistic effect of TNF and 2 topoisomerase-II-targeted drugs was evident in these human cell lines.
Int J Cancer 1990 Aug 15
PMID:Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines. 216 14

The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose-dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters.
Br J Cancer 1990 Sep
PMID:Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. 220 49

Activated carbon characteristically shows an extremely high transmigration to the lymph node, as well as a sustained release of the adsorbed drugs. Therefore, several attempts to use activated carbon as a carrier in cancer chemotherapy have been done. In the present study, we first introduced a new drug-dosage form of cisplatin (CDDP) adsorbed to activated carbon particles (CDDP-CH), and examined its characteristics and anti-cancer effect against human bladder cancer cell lines. CDDP solution of varied concentrations (Randa) was mixed with activated carbon particles (Norit A) and examined for adsorption and discharge by atomic absorption spectrophotometry and high performance liquid chromatography. Total CDDP adsorption increased in proportion to the amount of activated carbon. CDDP-CH was successfully prepared at an efficient concentration for cancer chemotherapy and CDDP-CH slowly discharged CDDP, indicating it as a useful means for the anti-cancer drug. Using cultured human bladder cancer cell lines (KU-1, HTB9), the anti-cancer effect was compared between CDDP and CDDP-CH by MTT-assay and double layer soft agar colony assay. CDDP-CH revealed an inhibitory effect against human bladder cancer cell lines. In view of the fact that activated carbon readily migrates to the lymph node, clinical application of this drug dosage form may be useful in cases of malignant tumor metastasis to the lymph node.
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PMID:[A study on cisplatin adsorbed to activated carbon particles as a new drug delivery system and its anti-cancer effect against human bladder cancer cell lines]. 223 25

Three human tumor cell lines of widely differing radiosensitivity were used to examine the characteristics of the 3-[4,5-dimethyl(thiazol-2-yl)-3,5-diphery]tetradium bromide (MTT) assay and to select suitable conditions for its use in assessing the response of cells to ionizing radiation. The optimal concentration of MTT and the time of incubation of the cells with MTT were individualized for each cell line. The relationship between absorbance and cell number was not linear over the wide range of cell numbers that were used. A calibration curve of absorbance against cell number for each cell line was therefore used. Using the assay to quantify metabolically viable cells, growth curves of irradiated and unirradiated cells were constructed on days 0-14 after irradiation. Accurate surviving fractions could be calculated only when cells were in exponential growth. Using this modification to its interpretation, the MTT assay was able to provide a reproducible measure of survival, which compared well with clonogenic cell survival measurements. However, the necessity to optimize conditions of the MTT assay for each cell line severely limits its usefulness in determining the radiosensitivity of cells in primary human tumor cultures.
Cancer Res 1990 Mar 01
PMID:Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation. 230 4

We applied the MTT dye reduction assay to the anti-cancer drug sensitivity test using short-term microplate cultures. Blast cells were cultured with approximately 25 anti-cancer drugs for 4 days. After cultivation, MTT dye was placed in each well, and the formazans generated by living cells were dissolved in acidified isopropyl alcohol. The absorbance of each well was measured at a scanning microplate photometer. When we made the table of the cytotoxicity index (CI) that was classified into anti-cancer drugs and concentrations for each leukemic sample, it was possible to compare efficacy with different drugs and to select the effective ones. Retrospectively, the in vitro results were compared with the clinical responses of the 34 patients (26 of acute lymphocytic leukemia [ALL] and eight of acute nonlymphoblastic leukemia [ANLL]) who were treated by combination chemotherapy. The following results were obtained: true-positive rate, 78.1%; true-negative rate, 57.1%; and predictive accuracy, 74.4%. Therefore, the MTT assay-CI table might serve as a reliable tool for the selection of effective chemotherapy in patients with acute leukemia.
Cancer 1990 Mar 15
PMID:An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia. 230 78

The Succinic Dehydrogenase Inhibition test (SDI test) has been widely used for a long time to evaluate the sensitivities of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed and the ability to make formazan improved through the use of MTT in this assay instead of TTC. Therefore, we modified SDI test in order to evaluate the drug response of gastrointestinal cancer and applied it in a clinical study. For the modification of the assay, we found it necessary to culture the cancer cells for three days and bring those cells in contact with MTT over a period of one hour. When we examined the sensitivities to anticancer agents at four different drug concentrations, if the cells were sensitive to the drugs, the optical densities were reduced according to the elevation of the drug concentrations. Further, we measured the drug concentrations in the blood of nude mice after the administration of anticancer drugs in the subrenal capsule assay which we developed previously. The drug concentration levels in the mice indicate the adequate drug dosage necessary to be effective in SDI test.
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PMID:[SDI test using MTT for the evaluation of drug sensitivities of gastrointestinal cancer cells]. 232 89


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