Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Integration of chemotherapy and radiation is the standard practice in the management of locally advanced inoperable NSCLC. To assess the biological interaction between third generation chemotherapeutic agents and radiation in non-small cell lung cancer (NSCLC) in vitro, we tested a number of different drugs (paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cisplatin) combined with radiation, in lung cancer cell lines. Cellular chemosensitivity was determined, using the semi-automated colorimetric MTT assay, after 48, 72 and 96 h of exposure to increasing drug concentrations, (0.001-100 microM) and radiation doses (100-400 cGy). Cell lines used were the adenocarcinoma (ADK), A-549, and the squamous-cell carcinoma (SCC), LX-1. Cells were pre-treated with anticancer agents at 24, 12 and 0 h before irradiation. Cytofluorimetric cell cycle analysis was performed. A significant S-phase block or a G(2)/M block was seen with gemcitabine and topotecan or paclitaxel pre-treatment, respectively. Apoptosis was seen only after paclitaxel exposure in the A-549 cell line. Despite a similar pattern of cell-kinetic changes induced by chemotherapy pre-treatment in all cell lines, the adenocarcinoma A-549 cell line was not radiosensitized by any of the anticancer agents tested, whereas synergism was observed in the LX-1 squamous carcinoma cell line, when exposed to gemcitabine, SN-38, topotecan and cisplatin. Paclitaxel, despite a favourable cell cycle effect, was not found to be synergistic with radiotherapy in our experimental model. In conclusion, the observed synergism appears to be dose- and timing-independent and seems to be related to the histological subtype being present in SCC only. Favourable perturbation of the cell cycle is evident with all the new agents tested in both cell types, but was not sufficient to produce synergism with radiation.
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PMID:Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines. 1142 93

Chemical modifications were performed on C-20 position of betulinic acid for a structure-activity relationship study. The evaluation of the compounds using human colon carcinoma HCT-116, human prostate adenocarcinoma PC3, and human melanoma cell lines M14-MEL, SK-MEL-2, and UACC-257 did not show any selective cytotoxicity towards melanoma cells. The results from both MTT reduction assay and SRB staining assay were comparable that no remarkable differences in cytotoxicity profile of the compounds were noticed. The C-20 position was found to be sensitive to the size and the electron density of the substituents in retaining the cytotoxicity of betulinic acid and was found to be undesirable position to derivatize.
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PMID:Development of C-20 modified betulinic acid derivatives as antitumor agents. 1152 42

Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.
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PMID:Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. 1167 77

Folate-polyethylene glycol-folate-grafted-polyethylenimine (FPF-g-PEI) was synthesized by linking folic acid to both ends of a mono-functional PEG and then grafting to PEI. The graft ratio was determined using Beer's law by measuring the UV absorbance at 363 nm. The pH profile, diameter and shape of the carriers were determined. Transfection efficiencies were optimized in normal smooth muscle cells (SMC) and CT-26 colon adenocarcinoma cells using plasmid DNA encoding luciferase reporter gene. Free folic acid was shown to inhibit transfection with FPF-2.3 g-PEI at neutral charge ratio. Relative toxicity between PEI and the modified carrier was measured using MTT colorimetric assay. Therapeutic potential of pmIFN-gamma complexed with these polymeric carriers in terms of gene expression was determined at protein and mRNA levels using ELISA and RT-PCR. FPF-g-PEI was determined to have 2.3 folate-PEG-folate (FPF) linear polymers grafted to each PEI molecule. The average molecular weight was measured to be approximately 33,500 Mw and the pH profile was characteristic of endosomal disruption capacity. Atomic Force Microscopy (AFM) and Dynamic Laser Light Scattering (DLLS) indicated FPF-2.3 g-PEI and PEI (at 2 w/w ratio) efficiently condensed plasmid DNA resulting in oblique spheroid polyplexes with a mean diameter of approximately 150 nm. FPF-2.3 g-PEI was superior to PEI in terms of cytotoxicity and transfection efficiency in cancer cells. Smooth muscle cells showed no specificity for folate tethered complexes, where PEI/pLuc complexes yielded higher efficiencies.
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PMID:Folate-PEG-folate-graft-polyethylenimine-based gene delivery. 1169 7

Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) is an interesting approach to detect and treat dysplasia and early cancers in the gastrointestinal tract. Because of low lipophilicity resulting in poor penetration across cell membranes, high doses of ALA should be administered in order to reach clinically relevant levels of PPIX. One way of increasing PPIX accumulation is derivatization of ALA into a more lipophilic molecule. In our in vitro study, different esterifications of ALA were investigated to analyze the effects on PPIX accumulation in human adenocarcinoma cell lines. For systematic analysis of cell type-specific PPIX accumulation, three human adenocarcinoma cell lines (SW480, HT29 and CaCo2) and a fibroblast cell line (CCD18) were tested. 3-(4,5-Dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were performed to ensure that the ALA esters showed no cellular dark toxicity. Different concentrations (ranging from 0.012 to 0.6 mmol/L, 3 h) and incubation times (5, 10, 30, 180 min; 0.12 mmol/L) were examined. PPIX accumulation was measured using flow cytometry. ALA esters, especially ALA-hexylester and ALA-benzylester, induced significant higher PPIX levels in adenocarcinoma cell lines when compared with ALA and may be promising candidates for PDT and PDD.
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PMID:The effects of 5-aminolevulinic acid esters on protoporphyrin IX production in human adenocarcinoma cell lines. 1172 1

AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.
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PMID:Regulatory effect and mechanism of gastrin and its antagonists on colorectal carcinoma. 1181 78

Folate-poly(ethylene glycol)-folate-grafted-polyethylenimine (FPF-g-PEI) was synthesized over a range of grafting ratios of folate-poly(ethylene glycol)-folate (FPF) to polyethylenimine (PEI). The conjugation was determined using the absorbance at 363 nm for each polymer. FPF-g-PEIs were determined to have 2.3, 5.2, 9.3 and 20 FPF linear polymers grafted to each PEI. The average molecular weight was calculated to be approximately 34,848, 47,266, 64,823 and 110,640 Da, respectively. The pH profiles of FPF-g-PEIs suggest that the polymers have endosomal disruption capacity, and the gel electrophoretic band retardation showed efficient condensation of DNA. The transfection efficiency, determined using plasmid encoding luciferase, was dependent on the cell type and was different for CT-26 colon adenocarcinoma, KB oral epidermoid, and normal smooth muscle cells (SMC). The relative toxicity of polymer/plasmid complexes was determined using the MTT colorimetric assay. At neutral charge ratio, FPF-g-PEI/pLuc complexes were less toxic to cells and showed higher transfection in cancer cells compared to PEI/pLuc complexes. Smooth muscle cells showed no specificity for FPF-g-PEI/pLuc complexes, whereas PEI/pLuc complexes showed a higher transfection efficiency. The transfection efficiency increased when neutral polymer/DNA complex concentrations increased, but decreased when positively charged polymer/DNA complex concentrations increased. There was little increase in toxicity when FPF-5.2g-PEI/pLuc complex concentrations increased.
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PMID:Optimization of factors influencing the transfection efficiency of folate-PEG-folate-graft-polyethylenimine. 1185 36

A series of Mannich ketones were synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antitumor activity. Substitutions were carried out with morpholinyl, pirrolidinyl, piperidyl and tetrahydro-isoquinolyl groups in various positions on three different skeletons. Lipophilicity of Mannich ketones was characterised by chromatography data (log k') and by software calculated parameters (clogP). Compounds were tested on their ability to inhibit the proliferation of the A431 human adenocarcinoma cell line evaluated by MTT and apoptosis assays. The results suggest that the higher the lipophilicity values (log k' and clogP), the higher the antitumor and apoptotic activity of Mannich ketones. Determination of lipophilicity by measuring the log k' or by calculating the clogP values of the compounds may help to predict their biological activities.
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PMID:Relationship between lipophilicity and antitumor activity of molecule library of Mannich ketones determined by high-performance liquid chromatography, clogP calculation and cytotoxicity test. 1188 64

Cisplatin is an important antineoplastic agent, but dose-limiting nephrotoxicity prevents potential efficacy. There is interest in developing new platinum agents that have less toxicity. We have synthesized novel platinum (II) coordination complexes containing diaminocyclohexane as carrier ligands, and glycolic acid as a leaving group. In this study, new platinum (II) complex compounds were evaluated for cytotoxicity on cancer cell lines and nephrotoxicity. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human ovarian adenocarcinoma cell lines (SKOV-3/NIH.OVCAR-3) and human prostate carcinoma cell lines (DU-145/PC-3). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be considerably less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.
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PMID:Anticancer cytotoxicity and nephrotoxicity of the new platinum (II) complexes containing diaminocyclohexane and glycolic acid. 1195 85

Histone deacetylase inhibitor (HDAI) induces accumulation of highly acetylated histones by inhibiting the activity of histone deacetylase and inhibits cell proliferation, induces differentiation, and promotes apoptosis. TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis in various human cancer cells, a promising observation because it raises the possibility of a death ligand selectively for tumor cells. However, resistance to TRAIL-induced apoptosis was seen in colonic adenocarcinoma cell lines. So we investigated whether human colonic adenocarcinoma cell lines can be sensitized to TRAIL-induced apoptosis by the addition of HDAI. We investigated sensitivity to histone deacetylase inhibitor in colonic adenocarcinoma cell lines using the MTT assay. Cell viability decreased with sodium butyrate (SB) and trichostatinA (TSA) in a dose-dependent manner in LS 180 and HT-29 cells. Nuclear condensation and fragmentation were observed by DAPI staining after 24 h stimulation with SB or TSA in LS 180 cells. We also investigated the combination of HDAI and TNF family members (TRAIL, anti-Fas antibody or TNFalpha) in colonic adenocarcinoma cell lines. HDAI augmented TNF family-related apoptosis in LS 180 cells and HT-29 cells. HDAI sensitizes human colonic adenocarcinoma cell lines to TRAIL-mediated apoptosis. HDAI may be useful as an adjuvant agent for TRAIL in the treatment of human colonic adenocarcinomas that are resistant to TRAIL.
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PMID:Histone deacetylase inhibitors sensitize human colonic adenocarcinoma cell lines to TNF-related apoptosis inducing ligand-mediated apoptosis. 1195 60


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