Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rapid colorimetric microtiter assay was used in this study to analysis drug cytotoxicity. Through the reduction of tetrazolium salt, MTT [3-(4, 5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide], by living cells to form a blue formazan product. The level of MTT cleavage by viable cells of various origins was found to be in direct proportion to the number of cells (between 500-10,000 cells/well). By MTT methods, the growth profile and chemosensitivity of 4 human tumor cell lines (KB, Hep-2, HA22T, and CoLo205) to 4 anticancer drugs (adriamycin, 5-fluorouracil, 6-mercaptopurine and cyclophosphamide) were assessed. Results from this assay were compared with data assimilated simultaneously by dye exclusion and clonogenic assay. In general, good correlation was observed among the clonogenic, dye exclusion and MTT assays for continuous drug exposures, yet the MTT assay was more rapid in testing in vitro chemosensitivity against human tumor cell lines. The dye exclusion assay was the most sensitive, followed by the clonogenic and then the MTT assays. The ID50 values obtained from the MTT assay were approximately 3 to 5 times lower than those from the other two methods. Based on these studies, MTT assay appears to be a rapid, convenient, economical and reasonable tool in the initial-stage screening of large number of the in vitro anticancer drugs.
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PMID:Evaluation of a rapid tetrazolium-based colorimetric assay for selecting anticancer drugs. 217 28

Conjunctivitis, mydriasis, corneal edema, lens luxation, buphthalmos, and blindness are caused by elevated IOP in the glaucomas. Primary glaucomas with a bilateral potential for development are noted in two cats and several dog breeds, with secondary glaucomas caused by uveitis and neoplasia common in the cat and dog. Tonometric evaluation is essential for the early diagnosis and management of glaucoma. Medical therapy of topical demecarium bromide and timolol maleate, with systemic dichlorphenamide, are recommended for general glaucoma maintenance therapy in dogs and cats. Transcleral cyclophotocoagulation will surgically reduce IOP in cases in which maximum medication has been reached.
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PMID:Glaucoma in the dog and cat. 219 58

In the present study, we characterized specific binding of bombesin (BBS)/gastrin-releasing peptide (GRP) to mouse colon cancer (MC-26) cells. MC-26 cells were inoculated into male BALB/c mice subdermally, and tumors were harvested from mice 21-28 days postinoculation. Tumor membranes were analyzed for binding to GRP-related peptides, using either 125I-GRP or 125I-tyrosine4-BBS. Under optimal binding assay conditions, BBS displaced specific binding of both 125I-GRP and 125I-tyrosine4-BBS in a dose-dependent manner, and a curvilinear displacement resulted. Specific binding data, analyzed by either a Scatchard or a Lineweaver-Burk plot, demonstrated presence of 2 classes of specific binding sites, arbitrarily named type I and type II sites. Type I sites had a high binding affinity [Kd 0.45 +/- 0.05 nM (SE)] and a relatively low capacity (226 +/- 27 fmol/mg membrane protein), whereas type II sites had a 10-20-fold lower binding affinity and approximately 6-7-fold higher capacity. BBS/GRP binding sites were specific for GRP-related peptides and demonstrated no significant binding affinity for all other unrelated peptides tested. Relative binding affinity of GRP analogues was in the order of GRP (14-27) greater than neuromedin C greater than or equal to BBS greater than or equal to GRP (1-27) greater than neuromedin B (for the later, P greater than 0.05 versus other peptides). Two BBS receptor antagonists, [D-Arg1,D-trp7,9,Leu11]-substance P (spantide) and [Leu13-psi-(CH2NH)Leu14]BBS also inhibited specific binding of 125I-GRP in a dose-dependent manner. Molecular weight of GRP/BBS binding proteins on tumor membranes was determined by cross-linking methods. A major molecular form (greater than 80-90%) (Mr approximately 75,000) and a minor Mr approximately 180,000 band were evident, both under reducing and nonreducing conditions. BBS (0.5-50 nM) demonstrated a significant dose-dependent growth effect on MC-26 cells in vitro, in terms of [3H]thymidine and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide uptake; these studies indicate that the BBS/GRP binding sites on MC-26 cells may serve as functional receptors and mediate the growth effects of BBS on MC-26 cells.
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PMID:Specific binding and growth effects of bombesin-related peptides on mouse colon cancer cells in vitro. 220 41

In vitro thermosensitivity of various human tumors including 90 esophageal, 10 gastric and 40 colo-rectal cancers were evaluated using the succinate dehydrogenase inhibition (SDI) test. Tumor fragments minced with scissors were incubated at 43 degrees C as heat treated cells and at 37 degrees C as controls for 20 hrs, and assayed for the succinate dehydrogenase (SD) activity using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as a hydrogen acceptor. The thermosensitivity was estimated by the percentage of SD activity of heat treated cells compared to that of each control. A variation in the thermosensitivity was noted between patients. The SD activity was 60.1 +/- 20.3% (mean +/- standard deviation) for esophageal cancers, 34.9 +/- 21.7% for gastric cancers, 50.3 +/- 20.6% for colo-rectal cancers. Significant differences were noted between esophageal cancers and gastric cancers, colo-rectal cancers (p less than 0.01 and p less than 0.05, respectively). When the thermosensitivity was arbitrarily defined as reduction in the SD activity to 50% of control or less, the positive rates were 31.1% for esophageal cancer, 70% for gastric cancer and 62.5% for colo-rectal cancer. Our results show that the SDI test is a useful method for determination of the thermosensitivity of clinical samples.
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PMID:[In vitro thermosensitivity of various human tumors evaluated using the SDI (succinate dehydrogenase inhibition) test]. 223 61

Southern blot hybridization analysis of clonal antigen receptor gene rearrangements has proved to be a valuable adjunct to conventional methods for diagnosing lymphoid neoplasia. However, Southern blot analysis suffers from a number of technical disadvantages, including the time necessary to obtain results, the use of radioactivity, and the susceptibility of the method to various artifacts. We have investigated an alternative approach for assessing the clonality of antigen receptor gene rearrangements in lymphoid tissue biopsy specimens. This approach involves the amplification of rearranged gamma T-cell receptor genes by the polymerase chain reaction and analysis of the polymerase chain reaction products by denaturing gradient gel electrophoresis. By use of this approach, clonal rearrangements from neoplastic lymphocytes constituting as little as 0.1-1% of the total cells in the tissue are detected as discrete bands in the denaturing gel after the gel is stained with ethidium bromide and viewed under ultraviolet light. In contrast, polyclonal rearrangements from reactive lymphocytes appear as a diffuse smear along the length of the gel. Our findings suggest that polymerase chain reaction combined with denaturing gradient gel electrophoresis may offer a rapid, nonradioactive, and sensitive alternative to Southern blot analysis for the diagnostic evaluation of lymphoid tissue biopsy specimens.
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PMID:Rapid, nonradioactive detection of clonal T-cell receptor gene rearrangements in lymphoid neoplasms. 223 63

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We previously reported HO-221 showed significant antitumor activities against various experimental tumor models, and was especially effective against the solid tumor. In this report we studied the mechanism of action of the compound. The inhibitory activity of HO-221 and 6 kinds of antitumor agents on DNA polymerase alpha was examined in vitro. HO-221 inhibited DNA polymerase alpha activity strongly. From the comparison with IC50 values of individual agents, the inhibitory activity of HO-221 was almost equivalent to aphidicolin and ara-CTP. By double reciprocal plot analysis, the inhibition of HO-221 was found to be non-competitive with the dCTP unlike that of aphidicolin and ara-CTP. Furthermore, HO-221 showed almost no effect on RNA polymerase activity and the protein synthesis. The effect of HO-221 on cell cycle progression of HL-60 cells was examined by flow cytometry analysis. The compound accumulated cells at S phase at a low concentration. The compound showed accumulation of cells in G1, G1-S and G2 + M phases. At higher concentrations, HO-221 increased the G1 phase of tumor cells, stopping the cell cycle progression. Therefore, G1 and S phase accumulation by HO-221 was considered to be correlated with the inhibition of DNA polymerase alpha dependent DNA synthesis. These results suggest that HO-221 is a novel antitumor agent with different mechanism of action from the known antitumor agents.
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PMID:[Mechanism of antitumor effect of a benzoylphenylurea derivative, HO-221]. 226 Aug 70

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
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PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71

Activated macrophages kill several types of tumor cells in vitro, whereas non-activated macrophages lack this capacity. We, however, observed that non-activated macrophages efficiently kill F9 teratocarcinoma as well as other teratocarcinoma cell lines. Dexamethasone, a glucocorticoid known to prevent macrophage activation, did not perturb the killing of F9 teratocarcinoma cells. Neither tumor necrosis factor alpha, nor the reactive oxygen intermediates, i.e. hydrogen peroxide, superoxide anion, and hydroxyl radical, nor serine proteases participated in this killing, shown by employing various agents which interfere with their production, secretion, or function. Using acridine orange/ethidium bromide vitality staining, the F9 teratocarcinoma cells were shown to be phagocytized alive by macrophages and subsequently killed intracellularly. Intact lysosomal function is required for the killing of F9 cells, as the lysosomotropic drugs chloroquine and ammonium chloride markedly inhibited this killing without perturbing their engulfment. The signal transduction pathway induced in the macrophages upon interaction with F9 teratocarcinoma cells seems to differ from that induced by macrophage activation. Neither the protein kinase C inhibitors polymyxin B and H-7 [1-(5-isoquinolinylsulfonyl)-2-methyl piperazine] nor the protein kinase C activator phorbol 12-myristate-13-acetate affected the killing of F9 cells. However, chlorpromazine (a powerful inhibitor of calmodulin), dibutyryl cAMP (a cAMP analog), and prostaglandin E2 inhibited the macrophage-mediated killing of F9 cells. In vivo studies indicate that an increased number of macrophages at the F9 tumor inoculation site (the peritoneal cavity) as a result of elicitation by thioglycollate prevents F9 tumor development. Our findings indicate that non-activated macrophages kill teratocarcinoma cells using a mechanism which differs from that employed by activated macrophages in the killing of other tumor cells.
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PMID:Engulfment and intracellular killing of F9 teratocarcinoma cells by non-activated murine macrophages. 227 89

The peptide gastrin has been shown to have growth stimulatory effects on normal as well as malignant gastrointestinal tissue. In this study, we have examined the possibility of autocrine growth-stimulation of cultured colon tumor cells by a gastrin-like peptide. The gastrin/CCK receptor antagonist dibutyryl cGMP inhibited the proliferation of two human colon carcinoma cell lines HCT 116 (EC50 = 1.3 mM) and CBS (EC50 = 2.5 mM) in a dose-dependent manner. Marked morphological changes were observed in HCT 116 cells after treatment with 1 mM dibutyryl cGMP. In receptor binding assays, dibutyryl cGMP competed with 125I-labeled gastrin for binding to HCT 116 cells (IC50 = 1.8 mM). Another derivative of cyclic GMP, 8-Bromo cGMP used as control due to its considerably weaker affinity for the gastrin/CCK receptor, did not compete with radiolabeled gastrin for binding to HCT 116 cells and had no effect on the morphology or proliferation in monolayer cultures of HCT 116 or CBS cells at concentrations up to 10 mM. Antigastrin/CCK antisera was also found to have dose-dependent cytostatic effects on HCT 116 and CBS cells adapted to growth in serum-free medium. The antiproliferative effect of the gastrin/CCK receptor antagonist and antigastrin/CCK antibodies suggested that a gastrin-like peptide secreted by these cells may promote growth. Radioimmunoassay of the conditioned medium of these two cell lines indicated the presence of a gastrin-like peptide (10-50 pg/10(6) cells/72 h). Northern analysis using an oligonucleotide DNA probe complementary to the nucleotide sequence coding the dodecapeptide carboxyl terminal of human gastrin showed three transcripts (0.7, 3.3, and 3.7 kb) that hybridized with the probe. These data provide, for the first time, evidence for an autocrine growth stimulatory role of a gastrin/CCK-like peptide in cultured colon tumor cells.
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PMID:Evidence for autocrine growth stimulation of cultured colon tumor cells by a gastrin/cholecystokinin-like peptide. 229 33

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.
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PMID:Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation. 230 4


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