UMLS:C0699790 - FACTA Search

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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated supra-additive cytotoxic effects of 5-fluorouracil (5FU) on gastric and colon cancer cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in vitro. p53 wild- and mutant-type gastric and colon cancer cell lines were treated by 5FU alone, TRAIL alone, and a combination of 5FU and TRAIL, and cell viability after each treatment was determined by MTT assay. The p53 wild-type cells were more sensitive to 5FU alone or to TRAIL alone than p53 mutant-type cells. The cell growth inhibitory effects of the combined treatment were supra-additive and more significant in proportion to the increasing concentrations of TRAIL as compared with 5FU alone both in p53 wild- and mutant-type cells. Furthermore, TRAIL could cause a decrease in 5FU IC(50) to within the range of clinically relevant doses, particularly in p53 wild-type cells. This is the first demonstration of the supra-additive antitumor activity of 5FU with TRAIL on gastric cancer cells, giving evidence that TRAIL can reduce the requirement for 5FU that ultimately results in minimizing risks for systemic side effects while increasing the antitumor activity of 5FU, suggesting the clinical applicability of this combination for gastric and colon cancers.
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PMID:Supra-additive antitumor activity of 5FU with tumor necrosis factor-related apoptosis-inducing ligand on gastric and colon cancers in vitro. 1216 12

DX-8951f or exatecan mesylate ((1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10-13(9H,15H)-dione methanesulfonate dihydrate), is a new water-soluble derivative of camptothecin. We determined the activity of DX-8951f in experimental human colon cancer and ovarian cancer, being tumor types sensitive to camptothecins. With the use of the MTT assay, DX-8951f was more potent than SN-38 in four out of five human colon cancer cell lines and three out of four human ovarian cancer cell lines (P<0.05). DX-8951f was considerably more potent than topotecan in all cell lines tested (P<0.05). Prolonged exposure to DX-8951f resulted in a greater increase in inhibition of cell proliferation as compared to that obtained with SN-38 or topotecan (P<0.05). Overexpression of Pgp, MRP1, and LRP did not affect the in vitro activity of DX-8951f. DX-8951f administered daily x 5 or weekly x 2 resulted in growth inhibition <50% in two human colon cancer xenografts grown s.c. in nude mice. In three human ovarian cancer xenografts, however, >50% growth inhibition was observed at both schedules. In the OVCAR-3 human ovarian cancer model, DX-8951f showed considerably greater activity than topotecan (P<0.01). DX-8951f combined with cisplatin or paclitaxel did not indicate the presence of a pharmacological interaction. In OVCAR-3 xenografts the combination was clearly more effective than DX-8951f alone, as the number of complete remissions increased substantially. In conclusion, this study shows that DX-8951f is highly potent in vitro and highly effective in experimental human ovarian cancer in vivo. Prolonged exposure to DX-8951f in vitro greatly increased the antiproliferative effects, which may be a rationale for testing a continuous infusion schedule in the clinic. Addition of cisplatin or paclitaxel improved the in vivo antitumor effects of DX-8951f.
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PMID:The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer. 1223 7

We examined the effects of suppressing multidrug resistance-associated protein (MRP) and multidrug resistance 1 (MDR1) gene expression in HCT-8DDP human colon cancer cell lines, which showed both cisplatin and multidrug resistance. Hammerhead ribozymes, designed to cleave MRP mRNA (anti-MRP Rz) and MDR1 mRNA (anti-MDR1 Rz), were transfected into the HCT-8DDP cells. Drug sensitivity was estimated by MTT assay in vitro. The HCT-8DDP/anti-MRP Rz cells were more sensitive to doxorubicin (DOX) and etoposide (VP-16) by 2.5- and 4.1-fold, respectively, compared with HCT-8DDP cells. The HCT-8DDP/anti-MDR Rz cells were more sensitive to DOX and VP-16 by 2.3- and 3.8-fold, respectively. The anti-MRP Rz and anti-MDR1 Rz significantly down-regulated resistance to DOX and VP-16, while anti-MRP Rz and anti-MDR1 Rz did not affect resistance to cisplatin, methotrexate and 5-fluorouracil. The hammerhead ribozyme-mediated specific suppression of MRP or MDR1 was sufficient to reverse multidrug resistance in the human colon cancer cell line.
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PMID:Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene. 1237 Jul 50

The pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1) is a heptahelical, G protein-coupled receptor that has been shown to be expressed by non-squamous lung cancer and breast cancer cell lines, and to be coupled to the growth of these tumors. We have previously shown that PACAP and its receptor, PAC1, are expressed in rat colonic tissue. In this study, we used polyclonal antibodies directed against the COOH terminal of PAC1, as well as fluorescently labeled PACAP, Fluor-PACAP, to demonstrate the expression of PAC1 on HCT8 human colonic tumor cells, using FACS analysis and confocal laser scanning microscopy. Similarly, anti-PACAP polyclonal antibodies were used to confirm the expression of PACAP hormone by this cell line. We then investigated the signal transduction properties of PAC1 in these tumor cells. PACAP-38 elevated intracellular cAMP levels in a dose-dependent manner, with a half-maximal (EC(50)) stimulation of approximately 3 nM. In addition, PACAP-38 stimulation caused an increase in cytosolic Ca(2+) concentration [Ca(2+)](i), which was partially inhibited by the PACAP antagonist, PACAP-(6-38). Finally, we studied the potential role of PACAP upon the growth of these tumor cells. We found that PACAP-38, but not VIP, increased the number of viable HCT8 cells, as measured by MTT activity. We also demonstrated that HCT8 cells expressed the Fas receptor (Fas-R/CD95), which was subsequently down-regulated upon activation with PACAP-38, further suggesting a possible role for PACAP in the growth and survival of these tumor cells. These data indicate that HCT8 human colon tumor cells express PAC1 and produce PACAP hormone. Furthermore, PAC1 activation is coupled to adenylate cyclase, increase cytosolic [Ca(2+)](i), and cellular proliferation. Therefore, PACAP is capable of increasing the number of viable cells and regulating Fas-R expression in a human colonic cancer cell line, suggesting that PACAP might play a role in the regulation of colon cancer growth and modulation of T lymphocyte anti-tumoral response via the Fas-R/Fas-L apoptotic pathway.
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PMID:PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumor cells. 1240 23

This study was designed to explore the possible interaction of 5-fluorouracil (5-FU) and 7-ethyl-10-hydroxycamptothecin (SN-38) in vitro. Human colon cancer LoVo cells were treated in both a dose- and time-dependent manner using clinically relevant concentrations of and exposure to 5-FU and/or SN-38. The expression of thymidylate synthase (TS), topoisomerase I, and cell cycle kinetics were evaluated by Western blot analysis and flow cytometry, respectively. Cytotoxicity was evaluated by MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide) assay. The cytotoxic effects of combination treatment were determined by median effect analysis. Topoisomerase I expression was downregulated following 12 hours of exposure to treatment, and topoisomerase I expression recovered 8 hours after SN-38 was removed. The TS expression was decreased following 24 hours of 5-FU and it remained at reduced levels for > 24 hours after removal of 5-FU. SN-38 induced an arrest at S/G2/M phase, reaching its maximum effect at 12 hours. This cell cycle arrest was reversed 24 hours after SN-38 was removed. 5-FU induced an arrest at the S phase, and maximum arrest occurred at 12 hours and lasted for > 48 hours. After 12 hours of sequential SN-38, LoVo cells were arrested in S phase, thereby potentiating the effect of 5-FU. Cytotoxicity studies confirmed the synergistic interaction between 5-FU and irinotecan. These findings suggest that the proper sequencing of 5-FU/irinotecan depends on regulation of topoisomerase I, and cell cycle kinetics
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PMID:Combination of 5-fluorouracil and irinotecan on modulation of thymidylate synthase and topoisomerase I expression and cell cycle regulation in human colon cancer LoVo cells: clinical relevance. 1248 36

Human thymidine phosphorylase (dThdPase) is an angiogenic factor identical to platelet-derived endothelial cell growth factor (PD-ECGF). Thymidine phosphorylase is also a converting enzyme of the prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU) in tumors. To assess the role of dThdPase in targeting chemotherapy, we examined the relationship between the expression of dThdPase and the sensitivity of 5'-DFUR in cancer cell lines, and also examined whether transfection of dThdPase cDNA enhanced the drug-sensitivity to 5'-DFUR with or without angiogenesis in breast cancer cells. Thirteen human cancer cell lines consisting of 4 breast cancer, 6 gastric cancer, and 3 colon cancer cell lines were used. Expression of dThdPase was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In vitro drug-sensitivity was assessed by MTT assay, and anti-tumor effect in vivo was assessed using nude mouse xenografts. Intratumoral microvessel density was evaluated by immunohistochemical staining to factor VIII related antigen. Transfection of dThdPase cDNA was performed using pcDNA3 expression vector encoding its cDNA by the lipofection method. An inverse relationship between the expression of dThdPase and the IC50 values of 5'-DFUR was observed (p=0.1278, rho=-0.440) in the 13 cancer cell lines. Transfection of dThdPase cDNA into MCF-7 breast cancer cells resulted in an approximately 2.6- and 10-fold increase of the expression of dThdPase mRNA and its enzyme activity, respectively, compared to the control vector alone. The sensitivity to 5'-DFUR in the transfected cells was increased approximately 20-fold compared to the parent cells and control vector alone, and the sensitivity to 5-FU was also somewhat increased. In contrast, the sensitivity to ADM, CDDP, and VP-16 was not different between the transfected and control cells. In nude mice xenografts of the transfected cells, treatment with 5'-DFUR had a significant anti-tumor effect compared to those of the untreated transfected cells and control vector alone treated with 5'-DFUR (p<0.01). Intratumoral microvessel density in the transfected cells was not significantly increased with or without treatment with 5'-DFUR compared to control vector alone. The high expression of dThdPase was correlated with an increase in the sensitivity to 5'-DFUR in gastrointestinal and breast cancer cell lines. The introduction of dThdPase cDNA in breast cancer cells enhanced the sensitivity to 5'-DFUR without an increase of tumor angiogenesis, and targeting chemotherapy of dThdPase may be a good tumor-specific and personalized therapy for improving the poor prognosis of cancer patients who show high expressions of dThdPase.
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PMID:Effects of introduction of dThdPase cDNA on sensitivity to 5'-deoxy-5-fluorouridine and tumor angiogenesis. 1263 76

There is still no therapy method in the colorectal cancers that is good enough for such a complex disease. Combined surgery, chemotherapy, and radiotherapy improved survival, but the side effects and the poor performance status of the patients seriously affect the use of these methods. We used a therapeutical approach of surgery and chemotherapy combined with biotherapy by Viscum album extract Isorel, aiming to improve the patients' resistance to the disease and to render the treatment's side effects more tolerable. Isorel is aqueous extract well known for its anticancer effects obtained by various in vitro and in vivo experimental models and which was validated by an in vitro bioassay on murine melanoma B16F10 and human cervical carcinoma HeLa cells. Isorel strongly reduced human colon cancer HT 29 cell line growth in vitro in the MTT bioassay. Hence, it was further used in a prospective, randomized, and controlled study which compared the postoperative results for patients with colorectal cancer stages Dukes C (40 patients) and D (24 patients) who, beside surgery, received either only chemotherapy (5-FU), 6 cycles (either the Mayo or the De Gramont protocol) or chemotherapy combined with Isorel biotherapy. These 64 patients were randomly allocated into three groups "only chemotherapy" for 21 cases, chemo + biotherapy for 29 cases and 14 patients underwent only surgery as the control group. We noted no toxic deaths due to either chemo or biotherapy. The patients operated on and treated with chemo and biotherapy had median survival significantly better and a cumulative proportion survival (Kaplan-Maier) superior to those of the patients receiving only postoperative chemotherapy. Thus, colorectal cancer patients seem to benefit in terms of survival from combined postoperative chemotherapy and Isorel biotherapy, either adjuvant or palliative.
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PMID:The influence of isorel on the advanced colorectal cancer. 1266 6

Acetylsalicylic acid (ASA) has been confirmed to inhibit proliferation and to induce apoptosis in human colorectal cancer cells in vitro. However, the mechanism by which ASA exhibits antiproliferative and proapoptotic effects in cyclooxygenase 2 (COX-2)-negative cells remains to be further elucidated. In the present study, SW480, a COX-2-negative colon cancer cell line, was treated with various concentrations of ASA (0, 2.5, 5, and 10 mM). The antiproliferative and proapoptotic effects of ASA were confirmed by MTT assay, flow cytometry of propidium iodide (PI)-stained cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. After treatment with ASA, intracellular cyclic AMP (cAMP) levels were increased and the production of prostaglandin E2 (PGE2) was decreased. RT-PCR analysis revealed that treatment of ASA induced a concentration-dependent downregulation of cytosolic phospholipase A2 (cPLA2) mRNA expression in SW480 cells and also in two other colorectal cancer cell lines, Colo320 and HT-29 cells. Intracellular calcium levels were unaffected by ASA treatment. Our results indicate that the ASA-induced downregulation of cytosolic phospholipase A2 mRNA expression might be a novel mechanism for ASA-mediated growth inhibition and apoptosis in colon cancer cells.
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PMID:Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells. 1283 97

The in vitro cytotoxic activity profile of nine novel phenylarsonic acid (CAS 98-05-5, PAA) compounds against 17 human cancer cell lines including (a) ovarian cancer cell lines ES-2, PA-1, CAOV-3, OVCAR-3, (b) testicular cancer cell lines Ntera-2, Tera-2, N2NICP, 833K, and 64CP, (c) multiple myeloma cell lines ARH77, HS-Sultan, RPMI-8226, and U266, and (d) acute lymphoblastic leukemia (ALL) cell lines NALM-6, MOLT-3, ALL-1, and RS4; 11, was determined by the MTT assay. The lead compounds, 2-methylthio-4-[(4'-aminophenylazo)-phenylarsonic acid] pyrimidine (PHI-370) and 2-methylthio-4-(4'-phenylarsonic acid)-aminopyrimidine (PHI-380) caused apoptotic death in all 17 cancer cell lines at low micromolar concentrations, as documented by TUNEL assays and confocal laser scanning microscopy. PHI-380 was also tested and found to be very active against primary tumor cells isolated from surgical biopsy specimens of 14 patients with therapy-refractory non-small cell lung cancer, breast cancer, colon cancer, lymphoma, hepatoblastoma, or Wilm's tumor as well. Because of their broad-spectrum and potent anticancer activity and ability to induce apoptosis in primary tumor cells from therapy-refractory cancer patients, PAA compounds such as PHI-370 and PHI-380 may provide the basis for effective salvage regimens for patients with recurrent cancer.
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PMID:Phenylarsonic acid compounds with broad-spectrum and potent cytotoxic activity against human cancer cells. 1287 14

The anticancer properties of zerumbone (2,6,9 humulatriene-8-one, a sesquiterpenoid) from Zingiber aromaticum were compared with those of curcumin from Curcuma longa in an in vitro MTT tetrazolium salt assay using HT-29, CaCo-2, and MCF-7 cancer cells and in an azoxymethane (AOM)-induced animal model of colon cancer using aberrant crypt foci (ACFs) as a preneoplastic marker. The IC50 of zerumbone was approximately 10 mM and that of curcumin was 25 mM. Cell cycle arrest in HT-29 cells was observed at G0/G1 for 10 and 12.5 mM and G2/M for 25 mM after 24 h at concentrations of 10-25 mM of zerumbone, and a concentration-dependent increase in apoptosis (2-6% of viable cells) was observed after 48 h using the same concentration range. Male Sprague-Dawley rats were fed extracts in an AIN diet prepared from the equivalent of 4% by weight of dried rhizomes of Z. aromaticum and C. longa. ACFs were induced by two doses (15 mg/kg body weight) subcutaneously of AOM 1 wk apart, the rats were killed 10 wk later, and the ACFs were assessed in the colon. Total ACFs were significantly reduced by Z. aromaticum extract (down 21%, P < 0.05) relative to control, the effect being most evident with large ACFs (>3 aberrant crypts per focus). Similar reductions were observed with 4% C. longa extract in the diet (down 24%, P < 0.01) and with 2,000 ppm curcumin, the effect being particularly evident with large ACFs. The concentration of zerumbone in the Z. aromaticum extract diet was assayed at 300 ppm and of curcumin in the C. longa extract diet was also 300 ppm, i.e., the extract of C. longa was as effective at one-seventh the concentration of curcumin as the positive control. Zerumbone is effective as an anticancer agent, possibly by its apoptosis-inducing and antiproliferative influences. This latter possibility is currently being investigated.
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PMID:Antitumor activity of extract of Zingiber aromaticum and its bioactive sesquiterpenoid zerumbone. 1288 Oct 17

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