Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic the in vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In these in vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P < 0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCS-H716 cell line alone but only at the highest concentration (10(-6) M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.
 ...
PMID:Omeprazole inhibits growth of cancer cell line of colonic origin. 762 78

Dithiane analogues of tiapamil are highly active as modifiers of P-glycoprotein mediated multidrug resistance (MDR) in vitro. In an assay using the P-glycoprotein over-expressing cell line KB-8-5, the most active analogues for decreasing vincristine resistance were the racemate Ro 11-5160 and its two enantiomers, Ro 44-5911 (R) and Ro 44-5912 (S). In the KB-8-5 assay, the resistance modification index (RMI) of Ro 11-5160 was approximately 12-fold higher than those of the most active reference compounds tested, dipyridamole, cepharanthine, reserpine and cyclosporin A, when compared at concentrations equal to one-tenth of the IC50 of each compound (RMI0.1). The enantiomers have similar resistance modifying activities, but the (S) enantiomer Ro 44-5912 is somewhat more active, fully reverting the vincristine sensitivity of KB-8-5 cells to the level of the parental KB-3-1 cells at a concentration of 2 microM. The (R) enantiomer attained this level of modification at a concentration of 3.5 microM. These concentrations are both well below their IC50 values for KB-8-5 cells (150 microM). The enantiomers appear to interact with P-glycoprotein because they inhibited [3H]azidopine and [3H]-vinblastine binding to plasma membrane fractions prepared from resistant K562/ADR cells. However, in addition to their resistance modifying activities with KB-8-5 cells, these compounds also decreased the IC50 values of vincristine and doxorubicin with KB-3-1 cells that do not express detectable levels of P-glycoprotein. Ro 44-5911 overcame doxorubicin and vincristine resistance in three colorectal cancer cell lines (DLD-1, WiDr and COLO 201) that express P-glycoprotein. No effect was seen with the 3 colorectal cell lines on the IC50 values of three drugs not related to the MDR phenotype, 5-fluorouracil, 5'-deoxy-5-fluorouridine and cis-diaminodichloroplatinum (II). The in vitro vasodilatory activity of these dithianes, measured with strips of rat aorta contracted with KCl, was about 5% of that of verapamil. These results suggest that diathianes could be useful agents for MDR modification in vivo.
 ...
PMID:Novel dithiane analogues of tiapamil with high activity to overcome multidrug resistance in vitro. 763 62

To confirm our previous kinetic analysis of the mode of cell-killing action of 5-fluorouracil (5-FU), we carried out a flow cytometric analysis with human colorectal cancer DLD-1 cells. Cells were treated with each cytotoxic concentration of 5-FU for 1 or 72 h, and the periodic changes in flow cytometric pattern were compared with those of 5-fluorouridine (FUrd) and 5-fluoro-2'-deoxyuridine (FdUrd). When cells were cultured with 5-FU for 72 h, most of them accumulated in S phase and remained there. This pattern was the same as that seen in cells that were continuously exposed to FdUrd. In contrast, when cells were exposed to 5-FU for 1 h and cultured in drug-free medium, they ended the cell-cycle traverse in either G2/M or G1 phase after an immediate but transient accumulation in S phase. Results were identical to those observed with cells similarly treated with FUrd. These results demonstrated a good accordance with those of our kinetic analysis, and strongly suggested that the mode of cell-killing exhibited by 5-FU differs with exposure time: 5-FU acts like FUrd in short exposure conditions, and it acts similarly to FdUrd in continuous exposure conditions.
 ...
PMID:Flow cytometric analysis of cell-killing actions of 5-fluorouracil in human colorectal cancer cells. 786 5

Several lines of evidence suggest that nonsteroidal antiinflammatory drugs may be effective in preventing colorectal cancer. These include animal experiments, case-control studies, and clinical experience with sulindac in promoting the regression of adenomatous colon polyps in adenomatous polyposis coli. We determined the antiproliferative activity of various nonsteroidal antiinflammatory drugs, including two sulindac derivatives, against human colon cancer cells in vitro. Ht-29, SW480, and DLD-1 cells were continuously incubated with serial drug dilutions for 6 days prior to fixation. Cell number was determined using the sulforhodamine B assay, and drug concentrations which inhibited cell growth by 50% were estimated for each agent by interpolation. All drugs exhibited antiproliferative activity against Ht-29 and DLD-1 cells, and most inhibited SW480 cells. For Ht-29 cells, the 50% inhibitory concentration varied from 55 microM for diclofenac to 2100 microM for 5-aminosalicylic acid, with three drug groups of high, intermediate, and low potency evident. Inhibition of cell growth by sulindac sulfide was reversible following drug removal. Nonsteroidal antiinflammatory drugs exert an antiproliferative effect against human colon cancer cells with a wide range of potencies. A cytostatic response was demonstrated with sulindac sulfide. These data further support the potential role of these agents for chemoprevention of colorectal neoplasia.
 ...
PMID:Antiproliferative effect of nonsteroidal antiinflammatory drugs against human colon cancer cells. 792 Feb 12

The therapeutic efficacy of 5-fluorouracil (5-FUra; 0.6 mg/day x 5 days) + leucovorin (LV; 1.8 mg/day x 5 days) and of 131I-labeled MN-14 anticarcinoembryonic antigen IgG (275 microCi single dose) was evaluated in size-matched (0.3-0.7 cm3) s.c. LoVo, HT-29, DLD-1, HCT-15, LS174T, and MOSER, GW-39, and WidR human colonic tumors. These lines express varying amounts of carcinoembryonic antigen and exhibit varying degrees of in vitro responsiveness to 5-FUra. Unlike radioimmunotherapy (RAIT), multiple cycles of chemotherapy were feasible over a 3-week period. However, no therapeutic advantage to a second cycle of 5-FUra/LV administration was found. Therefore, it is reasonable to compare single cycles of both treatment modalities. RAIT was statistically more effective in 5 of 8 tumor lines (LoVo, LS174T, MOSER, WidR, and GW-39). In 1 other line (DLD-1), RAIT was marginally more efficacious, but tumors responded well to both therapies. The lack of a statistical difference between the 2 modalities of treatment may indicate that the efficacy of the 2 treatments is equivalent, or the relatively large variability within the treatment groups may have prevented significance given the number of animals evaluated. RAIT and 5-FUra/LV were equally efficacious in the HT-29 and the HCT-15 tumor lines. Of the 5 xenografts that responded better to RAIT, 3 lines (LS174T, GW-39, and WidR) demonstrated a greater percentage of tumors responding over a 5- to 6-week period. The other 3 lines (LoVo, MOSER, and DLD-1) exhibited a similar percent of tumors responding to both therapies, but a greater growth inhibition in those RAIT-treated tumors that responded. In vitro responsiveness to 5-FUra/LV did not directly correlate with in vivo responsiveness (r2 = -0.664), since LS174T and LoVo tumors, with rapid growth rates (0.05-0.36 cm3/day), were not highly responsive to therapy. Growth inhibition from RAIT also did not correlate with total tumor carcinoembryonic antigen content (r2 = 0.003), an observation that may be due to additional variables, such as accessibility of antigen and innate radiosensitivity of the tumor. RAIT was most effective in the fastest growing tumor lines (LS174T, GW-39, MOSER, WidR, and LoVo). These preclinical results suggest an advantage to radioantibody therapy over one of the most commonly used forms of chemotherapy to treat colorectal cancer. These studies also highlight the need to establish criteria that will enable the selection of therapeutic modalities in patients.
 ...
PMID:Comparison of equitoxic radioimmunotherapy and chemotherapy in the treatment of human colonic cancer xenografts. 826 35

A new mutator mechanism for tumorigenesis, characterized by somatic genomic instability (SGI) at simple repeated sequences (SRS) or microsatellites, underlies hereditary nonpolyposis colorectal cancer (HNPCC) and some sporadic tumors of the colon and other types. To determine whether the microsatellite mutator phenotype (MMP) is dominant or recessive, we generate somatic cell hybrids between a tumor cell line without SGI at SRS (D98OR) and colon carcinoma cell lines with relative low (HCT-15) and high (LS174-T) SGI at SRS. The normal fidelity of replication of these unstable sequences was observed in each of these cell hybrids. Fusion of HCT-15/DLD-1 low instability cells, with LS174-T, HCT116 and LoVo cell lines, all exhibiting relative high instability, also restored the replication fidelity of SRS in all of the hybrids. Hybrids between the high instability cell lines did not grow possibly because of senescence or apoptosis. These results indicate that, in the cell lines analysed, the characterized mutator phenotype of the mismatch repair system resulting in high SGI at SRS, and the uncharacterized mutator phenotype underlying low SGI at SRS, are both recessive. The results also suggest that different tumor cells of the MMP harbor distinct altered growth-related genes.
 ...
PMID:The microsatellite mutator phenotype of colon cancer cells is often recessive. 857 Jan 81

We have determined the frequency and spectrum of spontaneous mutations at the hprt locus in LoVo, HCT116, LS180 and DLD-1 colon carcinoma cell lines exhibiting microsatellite genetic instability. Each cell line has a different mutator gene. LoVo and HCT116 cells have mutated hMSH2 and hMLH1 genes, respectively, which account for the majority of hereditary non-polyposis colorectal cancer (HNPCC). LS180 cells are wild type for these genes and also for hPMS1 and hPMS2 mismatch repair genes. DLD-1 cells harbor a mutated GTBP mismatch binding factor and a mutated DNA Polymerase delta. The mutation rate at the hprt locus was several hundred fold higher in these cell lines relative to control cell lines without microsatellite instability. The mutations were frameshifts (deletions and insertions of a single nucleotide in short repeats) and single base substitutions (transversions and transitions). Some mutations were shared by these four cell lines. However, every cell line also exhibited a distinctive spectrum of mutations suggesting that each mutator gene induces a particular mutator phenotype. These results also suggest that the frequency and spectrum of somatic mutations in tumor cells of the microsatellite mutator phenotype may have diagnostic applications to discriminate among the diverse underlying mutator genes.
 ...
PMID:Differences in the spectrum of spontaneous mutations in the hprt gene between tumor cells of the microsatellite mutator phenotype. 864 58

Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.
 ...
PMID:Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells. 908 68

Pulmonary side effects are increasingly observed as dose-limiting toxicity (DLT) of cancer treatment. The available preclinical models have a limited predictive value for lung toxicity in humans. We have attempted to elucidate potential mechanisms involved in these reactions, by studying the effects on cells, possibly involved in these reactions after in vitro exposure to drugs with known lung toxic effects. We have investigated the effects of bleomycin (BLM), mitomycin C (MMC), KW-2149 and its two known metabolites, M16 and M18, on oxygen radical production by granulocytes, on cytokine production: interleukin (IL)-6, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha by a human macrophage cell line (THP-1), by human endothelial cells (HVEC and HMEC) and a human colorectal cancer cell line (DLD-1), and on the cytotoxicity on endothelial cells in both confluent and non-confluent culture. The generation of oxygen radicals by normal and pre-stimulated granulocytes was not increased after preincubation with any of the drugs, at the concentrations tested. None of the cytokines (IL-6, TNF-alpha or TGF-beta) was found significantly increased in culture medium after exposure to any of the mitomycins. This was in contrast with the effect of BLM incubation, causing a rise in TGF-beta concentration. Both types of endothelial cells showed a dose-dependent, exposure duration-dependent, proliferation inhibition for all agents tested. This inhibitory effect was clearly proliferation dependent as shown by the increased inhibition in semi-confluent as opposed to confluent endothelial cell cultures. Both mitomycins tested were more cytotoxic than BLM to both confluent and proliferating endothelial cells.
 ...
PMID:In vitro toxicity studies with mitomycins and bleomycin on endothelial cells. 940 13

Recent advances in molecular biology have demonstrated that multistep genetic alterations are involved in the carcinogenesis of human colorectal cancer and that alteration of the p53 gene by mutation, deletion, or rearrangement is a major factor in this process. Human gene therapy has become a reality with the development of effective techniques for delivering the gene to the target cells. The efficacy of gene therapy for various types of genetic disease now being evaluated in clinical trials. These findings led us to develop a novel gene therapeutic strategy for human colorectal cancer that could replace the abnormal p53 gene using a recombinant, replication-defective adenoviral vector (termed Adp53). Infection with Adp53 induced rapid apoptotic cell death in DLD-1 and LoVo human colorectal cancer cell lines differing in their p53 status. Treatment with cisplatin following infection with Adp53 significantly suppressed the growth of WiDr colorectal cancer cells compared to single treatments alone. Thus restoration of wild-type p53 function exhibited an antitumor effect by inducing apoptosis as well as by markedly enhancing the effect of common chemotherapeutic agents in human colorectal cancer cells. In addition, Adp53 infection was antiangiogenic in SW620 human colorectal cancer cells. The application of this technology to human cancer therapy is now in progress. The article reviews recent highlights in this rapidly evolving field.
 ...
PMID:[Molecular surgery for human colorectal cancer with tumor suppressor p53 gene transfer]. 974 29


1 2 3 4 5 6 7 8 9 10 Next >>