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)

Cyclooxygenase (COX)-2 has been reported to play an important role in carcinogenesis. Meloxicam (preferential COX-2 inhibitor) inhibits the growth of COX-2 positive and COX-1 negative colorectal cancer cells. We evaluated the effects of meloxicam on the growth of lung cancer cells. By reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, COX-2 but not COX-1 was expressed in human non-small cell lung cancer (NSCLC) cell lines (A549 and PC14). In human small cell lung cancer (SCLC) cell line (H841), both COX-1 and COX-2 were not detected. MTT assay and prostaglandin (PG) E2 enzyme immunoassay showed that meloxicam inhibited the growth and PGE2 production of both A549 and PC14, but not H841 cells. These findings suggest that COX-2 may play an important role in the pathogenesis and progression of NSCLC, and that meloxicam may be a useful therapeutic agents in the treatment of NSCLC.
 ...
PMID:Meloxicam inhibits the growth of non-small cell lung cancer. 1106 95

The folate-dependent enzymes are attractive targets for cancer chemotherapy. Methotrexate (MTX), which inhibits dihydrofolate reductase, has been widely used for the treatment of solid tumors and hematological cancers. Raltitrexed ("Tomudex") ), which inhibits thymidylate synthase, is a novel anticancer agent active against colorectal cancer and some other solid tumors. We studied the optimal schedule of raltitrexed and MTX in combination against four human colon cancer cell lines Colo201, Colo320, LoVo, and WiDr. These cells were simultaneously exposed to raltitrexed and MTX for 24 h, or sequentially exposed to raltitrexed for 24 h followed by MTX for 24 h, or vice versa. Cell growth inhibition after 5 days was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of drug combinations at the concentrations of drug that produced 80% and 50% cell growth inhibition (IC(80) and IC(50)) were analyzed by the isobologram method (Steel and Peckham, 1979). Cytotoxic interactions between raltitrexed and MTX were schedule-dependent. The simultaneous exposure to raltitrexed and MTX showed additive effects in Colo201, LoVo and WiDr cells and antagonistic effects in Colo320 cells. The sequential exposure to raltitrexed followed by MTX produced additive effects in all four cell lines. The sequential exposure to MTX followed by raltitrexed produced synergistic effects in Colo201, LoVo and WiDr cells and additive effects in Colo320 cells. These findings suggest that the sequential administration of MTX followed by raltitrexed produces more than the expected cytotoxicity and may be the optimal schedule at the cellular level. Further in vivo and clinical studies will be necessary to determine the toxicity and to test the antitumor effects of sequential administration of MTX followed by raltitrexed proposed on the basis of the in vitro synergism.
 ...
PMID:Schedule-dependent synergism and antagonism between raltitrexed ("Tomudex") and methotrexate in human colon cancer cell lines in vitro. 1117 47

Raltitrexed (Tomudex) is a novel thymidylate synthase inhibitor with significant activity against advanced colorectal cancer. We studied the cytotoxic interactions of raltitrexed and 5-fluorouracil (5-FU) in four human colon cancer cell lines on various schedules. The cell growth inhibition after 5 days was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic interactions at the IC80 level were evaluated by the isobologram method. Simultaneous exposure to raltitrexed and 5-FU for 5 days produced additive to synergistic effects in Colo201 cells, and produced additive effects in Colo321, LoVo, and WiDr cells. Simultaneous exposure to raltitrexed and 5-FU for 24 h produced additive effects in Colo201, LoVo, and WiDr cells, and produced antagonistic effects in Colo320 cells. Sequential exposure to raltitrexed for 24 h followed by 5-FU for 24 h produced additive effects in Colo201, Colo320, and LoVo cells, and produced antagonistic effects in WiDr cells. The reverse sequence produced additive effects in Colo201 cells, and produced antagonistic effects in Colo320, LoVo, and WiDr cells. Simultaneous exposure to raltitrexed and 5-FU for 4 h and sequential exposure to raltitrexed for 4 h followed by 5-FU for 4 h with a 20-h interval produced additive effects, while the reverse sequence produced antagonistic effects in LoVo and WiDr cells. These findings suggest that the simultaneous administration of raltitrexed and 5-FU or the sequential administration of raltitrexed followed by 5-FU may be the optimal sequence, while the reverse sequence may be inappropriate. Preclinical and clinical studies of the simultaneous administration of raltitrexed and 5-FU and the sequential administration of raltitrexed followed by 5-FU are required to better understand the antitumor, toxic, and pharmacokinetic interactions of this combination in order to develop the combination chemotherapy of raltitrexed and 5-FU.
 ...
PMID:Schedule-dependent interaction between raltitrexed and 5-fluorouracil in human colon cancer cell lines in vitro. 1121 72

Prodigiosin is a red pigment produced by various bacteria including Serratia marcescens. Colorectal cancer is one of the most frequent malignancies and one of the most frequent causes of cancer death in the Western world. Its treatment is far from satisfactory and the challenge to oncologists is to find novel chemical entities with less toxicity and greater effectiveness than those used in current chemotherapy. Here we characterize the apoptotic action of prodigiosin in colon cancer cells. DLD-1 and SW-620 human colon adenocarcinoma cells, NRK and Swiss-3T3 nonmalignant cells were assayed by the MTT assay, fragmentation pattern of DNA, Hoechst 33342 staining and study of PARP cleavage by Western blot, in order to characterize the prodigiosin-induced apoptosis. Prodigiosin was purified and its structure was confirmed. Metastatic SW-620 cells were more sensitive to prodigiosin (IC50: 275 nM) than DLD-1. We did not observe a significant decrease in the viability of NRK cells. We confirmed that prodigiosin induces apoptosis in both cancer cell lines by the characteristic DNA laddering pattern and condensed nuclei or apoptotic bodies identified by fluorescence microscopy. These results indicate that prodigiosin induces apoptosis in colon cancer cells.
 ...
PMID:Prodigiosin-induced apoptosis in human colon cancer cells. 1138 4

YKL-40 (cartilage gp-39), is a mammalian glycoprotein related in sequence to chitinases. Its function is unknown, but it is thought to be involved in tissue remodeling. Immunocytochemical staining of YKL-40 in guinea pig chondrocytes (GPC), rabbit chondrocytes (RC), and rabbit synoviocytes (RS) was higher in dividing cells than in confluent cells, suggesting a participation of YKL-40 in cell cycle events. As assessed by the MTT assay, YKL-40 at 1.9-7.6 nM had dose-dependent mitogenic activity toward the three cell types. At 7.6 nM, YKL-40 increased the number of cells of 42% in GPC, 75% in RC, and 86% in RS after 72 h. YKL-40 also stimulated total proteoglycan synthesis by chondrocytes in a dose-dependent manner as assessed by Na[35SO4] incorporation and cetylpyridinium chloride precipitation. At 9.4 nM, YKL-40 increased proteoglycan synthesis of 42% in GPC and 58% in RC after 24 h. The growth factor properties of YKL-40 may explain the increased tissue remodeling associated with high levels of YKL-40 in joint diseases, and possibly, in malignant pathologies such as breast cancer or colorectal cancer.
 ...
PMID:YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes. 1146 40

AIM:To study the tumorigenicity of colorectal cancer cells transfected with B7 gene and the anti-tumor immunity induced by B7 gene modified colorectal cancer cells.METHODS:B7 gene was transfected into mouse colon cancer cell line CMT93.The transfectants were selected in DMEM containing 800mg/L G418, and B7 molecules were detected by immunohistochemistry.Experiments in vivo include: (1)5X10(6) B7(+) CMT93 cells were inoculated into the back of C57BL/6 mice subcutanously to determine their tumorigenicity (n = 4). As control, wild type CMT93 cells were inoculated the same as the experimental group (n= 3). (2) The mice primed by B7(+) CMT93 cells whose tumors vanished were rechallenged with wild type CMT93 to observe the immune protection of these mice against the wild type CMT93 (n = 4). Non-primed 4 native mice inoculated with wild type CMT93 were used as control.With in vivo cytotoxicity assay, the mice were immunized with B7 (+) CMT93 or the wild type CMT93 by intraperitoneal injection (n = 4X2). The spleen cells and the abdominal cavity infiltrating lymphocytes were obtained and cultured for two days. Cytotoxicity of these cells against the B7 gene modified or wild type CMT93 was detected by MTT assay.RESULTS:B7 high expression clones were obtained after the transfection of the B7 gene into CMT93 cells by electroporation. Immunohistochemistry results showed mainly membrance staining and partly cytoplasm staining in B7 gene transfected CMT93 cells. in vivo experiments: (1)After the inoculation of the B7(+) CMT93 cells in the back of C57BL/6 mice, they lost their tumorigenicity greatly (P < 0.01). All the small tumors growing in the early period in the experimental group vanished in one month, and the tumors in control group grew progressively. (2) No tumors were found in all 4 mice primed by B7(+) CMT93 cells after they were rechallenged with wild type CMT93. In the control group all mice had grown tumors (P < 0.05). In vitro cytotoxicity assay, the CTLs induced by B7(+) CMT93 had a higher cytotoxity against the wild type CMT93 than that induced by wild type CMT93 (P < 0.05), and the cytotoxity of CTLs induced by B7(+) CMT93 against B7(+) CMT93 cells was higher than that against wild type CMT93 cells (P < 0.05).CONCLUSION:The results suggest that the expression of costimulation B7 molecules by colorectal cancer cells can decrease their tumorigenicity greatly, and the B7 molecule can augment the activation of the CTLs against colorectal cancer, and it plays an important role in CTL effector function as well.
 ...
PMID:Expression of B7 costimulation molecules by colorectal cancer cells reducestumorigenicity and induces anti-tumor immunity. 1181 15

DNA topoisomerases (Topo) are enzymes that relieve the secondary twist on the DNA strand in the process of DNA synthesis and transcription; therefore they are unique targeting molecules for the chemotherapy of colorectal cancer. TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-in-deno [2,1-c]quinolin-7-one dihydrochloride, MW; 406.31), a novel quinoline derivative, has recently been established as a Topo I and Topo II inhibitor. The aim of the present study was to investigate the antitumor activity of TAS-103 by the MTT assay in human highly-purified and freshly-isolated colorectal cancer cells. To our knowledge, this is the first data concerning the antitumor activity of TAS-103 in highly-purified and isolated human colorectal cancer cells. TAS-103 showed the strongest antitumor activity among the conventional anticancer agents for colorectal cancer (p<0.05). The combination with CDDP augmented the antitumor activity of TAS-103 (p<0.05), indicating that CDDP is one of the most potent candidates to be used in combination with TAS-103. To predict the clinical effect of TAS-103, the expressions of Topo I and Topo II were measured by quantitative PCR. However, a correlation between the expression of Topo and the antitumor activity of TAS-103 was not established. In conclusion, according to this data, TAS-103 may be useful in the chemotherapy of colorectal cancer.
 ...
PMID:In vitro antitumor activity of TAS-103 against freshly-isolated human colorectal cancer. 1191 Dec 66

We report on the use of shock waves delivered by a shock-tube to permeabilize cancer cells and potentiate the cytotoxicity of the type-1 ribosome-inactivating protein, saporin. We studied human colorectal cancer HT29 and ovarian cancer OVCAR-5 cells, and used two different cytotoxicity assays, colony formation and loss of mitochondrial activity. A single shock wave and saporin (10(-9) M) produced significant toxicity not seen with either shock wave or drug alone. Increasing the number of shock waves up to five further increased cytotoxicity. Higher toxicity was seen with the clonogenic assay compared to MTT assay. Shock waves may have applications in promoting cytoplasmic delivery of toxins into cancer cells after intratumoral injection.
 ...
PMID:Delivery of ribosome-inactivating protein toxin into cancer cells with shock waves. 1244 79

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
Clin Colorectal Cancer 2002 Nov
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

We assessed the usefulness of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in the evaluation of appropriate adjuvant cancer chemotherapy for patients with advanced colorectal cancer. We analyzed 405 cases of colorectal cancer treated between January 1990 and August 1999 in terms of the MTT assay and survival outcome. Patients with Dukes' C and D were classified into a "surgery alone" group (n = 53), a "sensitive" group who received drugs that had a greater than 50% inhibition rate by MTT assay (n = 23), or "resistant"" group who were insensitive to the chemotherapy drugs (n = 124). Statistically significant differences in survival outcome were observed between the groups, with the sensitive group showing significantly better survival compared with the resistant group (p = 0.0158) and the surgery-alone group (p = 0.0004). Our results suggest that the MTT assay may be useful in evaluating the optimum adjuvant chemotherapy for patients with advanced colorectal cancer.
 ...
PMID:Clinical usefulness of chemosensitivity test for advanced colorectal cancer. 1253 38


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