Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse mAb M111 identifies a cell surface glycoprotein of 115,000 to 135,000 Da. M111 was expressed constitutively in subsets of cells of multiple lineages at discrete stages of cell maturation, suggesting that M111 is a differentiation Ag of the three germ layers. Ag expression could be induced by IFN-gamma but not by IFN-alpha, IFN-beta, or TNF. Induction of M111 expression was maximal at 48 h of culture in 200 U/ml of IFN-gamma and was independent of induction of class II MHC Ag. Induction was dependent on the cell type used. Nine colon cancer cell lines of undifferentiated phenotype were constitutively M111-; IFN-gamma induced M111 expression in seven of them. In contrast, IFN-gamma failed to induce M111 expression in six of six M111- ovarian cancer cell lines. Eight normal fibroblast cultures tested were M111-; they could not be induced to express M111. Three of five sarcoma cell lines were M111+; culture in IFN-gamma induced an increase in M111 expression in all of them. Constitutive and IFN-gamma-induced expression of M111 was independent of constitutive and induced expression of HLA class I and II molecules. IFN-gamma-mediated induction of M111 expression was not accompanied by coordinate changes in the expression of other differentiation traits. These results suggest that expression of the M111 gene is controlled by two mechanisms, one related to differentiation and the other activated by IFN-gamma.
 ...
PMID:IFN-gamma-regulated expression of a differentiation antigen of human cells. 312 30

A synergistic antitumor effect of natural human tumor necrosis factor-beta (TNF-beta) in combination with hyperthermia was found, in comparison with that of TNF-alpha, using an in vitro antiproliferative assay on a human colon cancer cell line (RPMI4788) and an in vivo tumor growth inhibition assay on Meth A sarcoma cells. In vitro combined treatment with TNF-beta (10,000 U/ml) and hyperthermia (at 43 degrees for 60 min) synergistically inhibited the proliferation of the cells. Combined effects of TNF-alpha or natural human interferon-alpha or -gamma (IFN-alpha, -gamma) and hyperthermia were also examined, and furthermore, the combinations of TNFs and IFNs were examined in combination with hyperthermia at 42 degrees; their antiproliferative effects were further augmented by hyperthermia. In vivo growth of Meth A sarcoma cells (5 x 10(5)), transplanted subcutaneously into BALB/c mice, was inhibited significantly (P less than 0.05) with the combination of TNF-alpha or -beta (2 x 10(5) U/mouse) and hyperthermia (at 43 degrees for 60 min) as compared to either a single intravenous injection of TNF-alpha or -beta alone or the hyperthermia alone. The influence of TNF-beta and hyperthermia on the cell cycle was examined. Flow cytometric analysis showed that RPMI4788 cells treated with TNF-alpha or -beta accumulated in the S phase of the cell cycle, and that hyperthermia (at 42 degrees for 60 min) alone had no influence on the cell cycle and did not augment the S phase accumulation of the cells treated with TNF-alpha or -beta.
 ...
PMID:Hyperthermic enhancement of the antitumor effect of natural human tumor necrosis factor-alpha and -beta: an in vitro and in vivo study. 314 36

Recombinant human interferon alpha inhibits growth of a human colon cancer cell line, Colo 205. To explore the mechanisms of IFN induced growth inhibition, quiescent Colo 205 cells were stimulated to proliferate in serum-free media by defined growth factors. Addition of insulin, transferrin and selenium (ITS) stimulated DNA synthesis, as measured by 3H-thymidine incorporation, in a dose-dependent manner. IFN-alpha (at concentrations greater than 100 U ml-1) inhibited ITS stimulated DNA synthesis by 63%. Inhibition of cell cycle traverse was confirmed by flow cytometric analysis. Although IFN inhibited growth of ITS-treated cells, steady state levels of c-myc mRNA remained above levels observed in unstimulated cells. IFN inhibited DNA synthesis only when added prior to mitogen stimulation. IFN, added 6 h after exposure of quiescent cells to ITS, failed to inhibit cell growth. Addition of increasing concentrations of ITS failed to overcome the IFN-induced growth inhibition. These results suggest IFN may inhibit cell growth in part by antagonizing the action of growth factors.
 ...
PMID:Inhibition of mitogen stimulated growth of human colon cancer cells by interferon. 316 5

Interferon-alpha (IFN alpha) potentiates the antitumor activity of 5-fluorouracil (FUra) in colon cancer in vitro, in vivo, and clinically. A likely mechanism for this action is the induction by IFN alpha of thymidine phosphorylase (TP), the first enzyme in one pathway for the metabolic activation of FUra to fluorodeoxyribonucleotides. To test this hypothesis, an expression vector containing the TP cDNA was transfected into HT-29 human colon carcinoma cells. Five stable transfectants were selected and analyzed. All showed increased sensitivity to FUra cytotoxicity, ranging from a 2-fold to a 19-fold decrease in the IC50 for FUra, compared to wild-type cells. Levels of TP mRNA, protein, and enzyme activity were elevated in the transfectants, and there was a significant correlation between the relative increase in sensitivity to FUra and both the increase in both TP mRNA levels and TP activity. Transfected cells exhibited increased formation of FdUMP, but not the ribonucleotides FUDP and FUTP, from FUra when compared to wild-type cells. The changes in TP activity, FdUMP formation, and FUra sensitivity in the transfected cells were comparable with those seen after treatment of wild-type cells with IFN alpha. These studies provide direct evidence for the role of TP in mediating the sensitivity of colon carcinoma cells to FUra, and further support the importance of the induction of TP in the biomodulating action of IFN alpha on FUra chemosensitivity.
 ...
PMID:Thymidine phosphorylase mediates the sensitivity of human colon carcinoma cells to 5-fluorouracil. 764 71

In order to select a suitable combination chemotherapy with BOF-A2 from the view of both anti-tumor effect (IR) and decrease of side effect, we studied a combination significance of BOF-A2 with CPT-11 that promised for a new anticancer drug, CDDP or mitomycin C (MMC) that used widely to many cancer patients and interferon-alpha (IFN-alpha) against colon, stomach and renal cancer, respectively, by using xenografted nude mice. The combination therapy of BOF-A2 with CDDP was effective against stomach cancer (H-111) from the cellular change and decreased side effect. The combination therapy of BOF-A2 with MMC showed additive effect against stomach cancer (H-111) from IR and cellular changes. The combination effect of BOF-A2 with IFN-alpha was additive and synergistic against renal cancer (H-12). The combination therapy with CPT-11 was effective (IR > or = to 58%) from antitumor effect, additive from IR and synergistic from cellular change against lung cancer (H-74) and colon cancer (H-110), to which conventional drugs were generally insensitive and spontaneously tolerant. BOF-A2 was expected to be a promising new anti-cancer agent in the future clinical trial.
 ...
PMID:[Combination chemotherapy of BOF-A2, a new 5-FU derivative, with various anticancer agents against human cancer xenografts in nude mice]. 806 Jan 37

We have previously shown that a short course of recombinant interferon-alpha-2b (rIFN-alpha-2b) (3 million units day for 5 days) for patients with primary gynaecologic malignancies was able to increase the circulating levels of a newly discovered tumour associated antigen, termed 90K. In this study, we have investigated the effects of the same modality of administration of rIFN-alpha-2b in 62 patients with breast and colorectal cancer whose primary tumour was surgically removed 1 month before and who were without evidence of disease (NED) at the time of the study. A significant increase of 90K serum concentration was already observed 24 h after the first r-IFN-alpha-2b injection and persisted throughout the investigational period. The increase was more pronounced in patients with a basal 90K-negative than a 90K-positive assay. Of 54 patients who started the test with a 90K negative assay, 17 (31%) shifted to a positive assay after rIFN-alpha-2b. Twenty-eight of 62 (45%) patients exhibited a 90K value above the mean increment of the whole population. The serum levels of CEA, CA-15-3, CA 19-9, and alpha-fetoprotein measured in the same serum samples were not modified. After 2 years of follow-up, ten patients relapsed. Six of them showed a 90K increase above the mean increment of the whole population. As with ovarian cancer, the increase of 90K following r-IFN-alpha-2b administration might be of importance for the early detection of disease recurrence in clinically NED breast and colon cancer patients.
 ...
PMID:Dynamic test with recombinant interferon-alpha-2b: effect on 90K and other tumour-associated antigens in cancer patients without evidence of disease. 843 5

We have previously reported that interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blocked the cell cycle progression of cancer cells at the S to G2 transition, causing a synergistic antitumor effect. In this study, the combined effects of both these cytokines and 5-fluorouracil (FUra) on tumor growth and cell cycle progression were investigated in a human colon cancer cell line, RPMI 4788, transplanted in CD-1 nude mice. Daily administration of IFN-alpha and TNF-alpha for 21 days markedly suppressed the tumor growth and induced cytokinetic alterations in which S phase cells were increased and cells in G2/M phase were decreased. FUra added to these cytokines further suppressed tumor development but did not affect the cytokinetics further. Combination of FUra and cytokines in a low dose, either of which alone had no effect, suppressed the tumor growth. These findings demonstrate that IFN-alpha, TNF-alpha and FUra have a distinct antitumor effect in combination.
 ...
PMID:Anti-proliferative and cytokinetic effects of tumor necrosis factor-alpha, interferon-alpha and 5-fluorouracil on a human tumor xenograft. 857 82

Interferon-alpha (IFN-alpha) exhibits synergistic antitumor activity when combined with tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo and increases the cytotoxicity of 5-fluorouracil (5-FU) in vitro. Using a colon cancer cell line transplanted into nude mice, we examined the effects of pretreatment for 3 days with IFN-alpha (10(6) IU) and/or TNF-alpha (2.9 x 10(3) JRU) on 5-FU metabolism. 5-FU 30 mg/kg was administered after the pretreatment. IFN-alpha increased the tumor level of 5-fluorodeoxuridine monophosphate (FdUMP), and decreased the free level of thymidylate synthetase. Pretreatment with TNT-alpha alone decreased HUMP whereas TNF-alpha plus IFN-alpha abolished the enhancement of FdUMP production by IFN-alpha. TNF-alpha also suppressed thymidine kinase activity. Neither IFN-alpha nor TNF-alpha altered the incorporation of 5-FU into RNA.
 ...
PMID:Suppressive effect of TNF-alpha on increased production of FdUMP by IFN-alpha. 868 Jul 97

The activity of the synthetic somatostatin analogue SMS 201-995 was investigated in vitro on the growth of SW480 and SW620 human colon adenocarcinoma cell lines. The inhibition of cell proliferation was significant in SW480 cells (-19.6 +/- 1.4% at SMS 201-995 10-9 M, P < 0.05), but not in SW620 cells (-5.5 +/- 0.8% at SMS 201-995 10-8 M) as compared to untreated cultures. Moreover, SMS 201-995 10-8 M decreased the mitogenic effect of epidermal growth factor (EGF) on the SW480 cell line (-26.6 +/- 3.4% vs. cells exposed to EGF 10 ng ml-1 alone, P < 0.05). The effect of combining SMS 201-995 plus the cytokines interleukin-2 (IL-2) or gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell growth was also evaluated. The treatment produced a synergistic antiproliferative effect against SW620 cells as compared to untreated cultures, with growth inhibition being -20.2 +/- 1.2 and -19.3 +/- 1.3%, at SMS 201-995 10-8 M plus IL-2 or gamma-IFN 100 IU ml-1, respectively, but did not increase the activity of SMS 201-995 against the SW480 cells. In conclusion, the effect of SMS 201-995 on colon cancer cell growth can be enhanced by its combination with cytokines in SW620 but not in SW480 colon adenocarcinoma cells.
 ...
PMID:Inhibitory effect of the somatostatin analogue SMS 201-995 and cytokines on the proliferation of human colon adenocarcinoma cell lines. 874 43

In order to investigate the combined antitumor activity of 5-fluorouracil (5-FU), and recombinant human interferon alpha 2a (IFN alpha) or human fibroblastoid interferon beta (IFN beta), the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was carried out using a cultured human colon cancer cell line (C-1) and fresh surgical specimens of gastric and colon carcinomas. IFNs did not show positive antitumor activity against C-1 cells, whereas 5-FU showed time- and concentration-dependent antitumor activity against C-1 cells. Furthermore, the antitumor activity of 5-FU on C-1 cells was augmented by IFN alpha or beta. When 5-FU (50 micrograms/ml) with IFN alpha (50 IU/ml). or IFN beta (50 IU/ml) was applied for the MTT assay with 48 hours incubation of fresh surgical specimens of gastric and colon carcinomas, the inhibition rates increased by 10% in 9 of 21 gastric specimens and in 18 of 36 colon carcinomas for IFN alpha (47.4% or 27/57), and in 8 of 15 gastric specimens and in 15 of 28 colon carcinomas for IFN beta (53.5% or 23/43). These results suggest that the chemosensitivity to 5-FU of human gastric and colon carcinomas is increased in the presence of IFNs, without involvement of the host-mediated immune system, and that this combined effect can be predicted by the MTT assay in vitro.
 ...
PMID:Interferons alpha-2a and beta increase the antitumor activity, detected by MTT assay, of 5-fluorouracil against experimental and clinical human gastrointestinal carcinomas. 906 9


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