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

Colon carcinoma is one of the most frequent causes of cancer death in industrialized countries. The patients generally die of the metastases. In a colon cancer rat model, the authors have shown that lipopolysaccharides from Escherichia coli induced the regression of carcinomatosis and cured 20%-30% of the rats. Some synthetic derivatives of lipid A, which are less toxic than lipopolysaccharides, were injected 14 days after the tumor cells. They induced the complete regression of peritoneal carcinomatosis consisting of numerous nodules measuring 1-5 mm in 20%-30% of rats. Only compounds with three or more hydroxymyristic acid residues were effective. In vivo effects were correlated with the capacity to induce the production of interleukin 1 and tumor necrosis factor but not with the capacity to induce macrophage-mediated cytolysis. It is therefore possible to synthesize weakly toxic derivatives of lipopolysaccharides retaining their antitumoral property in vivo.
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PMID:Antitumor effect of synthetic derivatives of lipid A in an experimental model of colon cancer in the rat. 186 Jun 36

The effect of recombinant human interleukin 4 (IL-4) on the expression of antitumor activity of human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined. AM were incubated for 16 h in medium with various macrophage activators [lipopolysaccharide, des-methyl muramyldipeptide, Nocardia rubra cell wall skeleton, and heptanoyl-gamma-D-Glu-(L)-meso-alpha,epsilon-A2pm(L)-D-Al aOH] in the presence or absence of IL-4, and then their tumoricidal activity was assayed by measuring 125I-UdR release from human melanoma (A375) cells. The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4 in 3 of 7 donors. Addition of IL-4 to cultures of AM with the activators resulted in dose-dependent suppression of AM-mediated cytotoxicity against A375 cells. IL-4 also inhibited AM-mediated cytotoxicity against A375-R cells, which are resistant to interleukin 1 (IL-1) and tumor necrosis factor alpha, HT-29 colon cancer cells, and KB cells. IL-4 inhibited the early induction phase of AM activation. Pretreatment of AM with IL-4 also suppressed their expression of antitumor activity in response to lipopolysaccharide. IL-4 inhibited the production of monokines (IL-1 and tumor necrosis factor alpha) by AM at the protein and mRNA levels. These findings suggest that IL-4 may be important in vivo in the down-regulation of antitumor expression of AM in the lung by inhibiting the production of monokines and other killing mechanisms.
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PMID:Down-regulation by interleukin 4 of activation of human alveolar macrophages to the tumoricidal state. 191 71

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated antitumor monokine(s) in response to activation stimuli such as various types of interferon (IFN) and/or synthetic desmethyl muramyl dipeptide (norMDP). IFNs (alpha, beta, and gamma) and norMDP rendered blood monocytes cytotoxic to allogeneic A375 melanoma cells, as assayed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells. This membrane-associated antitumor monokine induced by the synergistic actions of suboptimal concentrations of IFN-gamma and norMDP, was cytotoxic to HT-29 colon cancer cells as well as A375 melanoma cells, but not to actinomycin D-treated L-929 cells. The fixed monocyte-mediated cytotoxicity against A375 melanoma cells was completely inhibited by a specific anti-interleukin 1 alpha antiserum, but not by a specific anti-interleukin 1 beta antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated interleukin 1 alpha is involved through cell-to-cell contact in the host defense mechanism against cancer.
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PMID:Membrane-associated interleukin 1 alpha as a mediator of tumor cell killing by human blood monocytes fixed with paraformaldehyde. 246 72

The mechanisms of immunosuppression induced by colon cancer in rats were investigated at the systemic and tumor levels. During tumor growth (after i.p. injection of rat colon adenocarcinoma cells in syngeneic BD IX rats), Con A-induced proliferation of splenic mononuclear cells decreased and nitric oxide (NO) production by splenic macrophages increased concomitantly. Incubating splenic mononuclear cells with an inhibitor of NO synthase, NG-monomethyl-L-arginine, restored lymphocyte proliferation. A low level of inducible NO synthase mRNA was detectable in tumors by Northern blotting, with a weak increase during tumor growth. The NO concentration measured in the tumor nodules increased weakly parallel to the tumor growth. Five and six weeks after tumor cell injection, tumor-infiltrating lymphocytes from disaggregated tumors did not proliferate in the presence of Con A. Addition of NG-monomethyl-L-arginine inhibited the production of NO in tumor dissociations and enhanced tumor-infiltrating lymphocyte proliferation. Glyceryl trinitrate (a NO-releasing compound) totally inhibited the lymphocyte proliferation in vitro while it slightly reduced the tumor cell proliferation. T lymphocytes were therefore more sensitive to NO than were tumor cells. Culture medium from tumor cells induced NO production by splenic macrophages, although the factor involved has not yet been identified. Furthermore, tumor cells could also play a part in NO production by tumors because the tumor cells were induced to produce NO by IFN-gamma plus IL-1. These results strongly suggest the participation of NO in the tumor-induced immunosuppression in rats.
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PMID:Nitric oxide involvement in tumor-induced immunosuppression. 751 29

We have previously demonstrated that in vivo activation or inhibition of Kupffer cell (KC) cytotoxic function can reduce or enhance, respectively, the hepatic tumor burden in a syngeneic murine colon adenocarcinoma (MCA26) tumor model. In the current study, we have performed in vitro experiments to define the possible mechanisms of KC cytotoxicity against MCA26 cells. Addition of either anti-tumor necrosis factor (TNF) or anti-interleukin-1 alpha (IL-1 alpha) antisera reduced KC cytotoxicity in coculture against MCA26 targets in a dose-dependent fashion; addition of these sera together resulted in approximately additive inhibition, suggesting the existence of parallel pathways for these effector molecules. Nitric oxide as a mediator of cytotoxicity by KCs in coculture with MCA26 cells was evaluated by two approaches. Activated KCs produced detectable levels of nitric oxide; however, activated KC exerted cytotoxicity against MCA26 targets in the absence of exogenous free L-arginine. Thus, TNF and IL-1 play major roles in producing murine KC cytotoxicity against MCA26 colon cancer cells in vitro, whereas reactive nitric oxides do not.
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PMID:Mechanisms of Kupffer cell cytotoxicity in vitro against the syngeneic murine colon adenocarcinoma line MCA26. 831 55

Binding of colon cancer to extracellular matrix (ECM) proteins and mesenchymal cells that comprise the basement membrane is important in migration and metastasis. This study defines the conditions and surface structures necessary for adhesion of HT-29 cells to ECM proteins and cell monolayers. Binding began within minutes and peaked by 1 hr, with 80-95% of HT-29 cells binding to the ECM proteins, collagen IV, laminin, fibronectin, and vitronectin and 40-75% binding to monolayers of fibroblasts, smooth muscle cells, and HT-29 cells. Treating mesenchymal cells with the fibrogenic cytokines, IL-1, IL-4, or TNF-alpha, which increase production of ECM proteins, did not alter binding of HT-29 cells to these monolayers. Attachment of HT-29 cells to cell monolayers was inhibited by cytochalasin D and sodium azide, but not cycloheximide or neuraminidase. Attachment to ECM proteins, in contrast, was unaffected by any of these metabolic inhibitors but required certain divalent cations (Mg2+ and Mn2+ but not Ca2+). Antibody to the integrin beta 1, chain (CD29) eliminated binding to collagen and laminin but not to fibronectin, fibroblasts, and HT-29 monolayers. Antibody to the vitronectin receptor inhibited binding to fibronectin. Antibodies to integrin alpha 1-alpha 6 chains had no effect on any adhesion event. Three colon cancer cell lines were tested for expression of VLA antigens: alpha 2 and alpha 3 were detected on all three, alpha 1 and alpha 6 were variably expressed, while alpha 4 and alpha 5 were absent. This study demonstrates that several mechanisms account for tumor cell attachment to substratum and cells.
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PMID:Mechanisms of colon cancer binding to substratum and cells. 876 78

It has been proposed that cyclooxygenase (COX)-1 and COX-2 subserve different physiologic functions largely because of the striking differences in their tissue expression and regulation. COX-1 displays the characteristics of a "housekeeping" gene and is constitutively expressed in almost all tissues. COX-1 appears to be responsible for the production of prostaglandins (PG) that are important for homeostatic functions, such as maintaining the integrity of the gastric mucosa, mediating normal platelet function, and regulating renal blood flow. In sharp contrast, COX-2 is the product of an "immediate-early" gene that is rapidly inducible and tightly regulated. Under basal conditions, COX-2 expression is highly restricted; however, COX-2 is dramatically upregulated during inflammation. For example, synovial tissues in patients with rheumatoid arthritis (RA) express increased levels of COX-2. In animal models of inflammatory arthritis, COX-2 increases in parallel with PG production and clinical inflammation. In vitro experiments have revealed increased COX-2 expression after stimulation with proinflammatory cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), in many cell types, including synoviocytes, endothelial cells, chondrocytes, osteoblasts, and monocytes/macrophages. Another distinguishing characteristic of COX-2 is decreased expression in response to glucocorticoids. COX-2 is also increased in some types of human cancers, particularly colon cancer. Mechanisms underlying the association between COX-2 overexpression and tumorigenic potential may include resistance to apoptosis, or programmed cell death. Upregulated COX-2 expression undoubtedly plays a role in pathologic processes characterized by increased local PG production. One would predict, based on current information regarding the differential tissue expression of COX-1 and COX-2, that highly selective inhibitors of COX-2 will provide effective antiinflammatory activity with marked reduction in toxicity.
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PMID:COX-1 and COX-2 tissue expression: implications and predictions. 924 46

We previously reported that intracolonic administration of enprostil, a prostaglandin-E(2) (PGE(2)) analogue, had therapeutic effects on acute colitis induced in rodents by dextran sulfate sodium (DSS). In addition, production of growth-regulated gene product/cytokine-induced neutrophil chemoattractant-1 [GRO/CINC-1; an interleukin(IL)-8 like cytokine] was suppressed in the inflamed tissues. In the present study we used a human colon cancer cell line (HT-29) to investigate enprostil effects on the IL-8 production of intestinal epithelial cells stimulated by various stimulants. In a MTT assay, concentrations of enprostil >10(-5)M had cytotoxitic effects on HT-29 cells. Furthermore, 10(-6) M enprostil suppressed IL-8 production in HT-29 cells, SW620 and CaCo2 stimulated with interleukin-1 beta (IL-1 beta) or lipopolysaccharide (LPS), but did not suppress this response when cells were stimulated with tumour necrosis factor (TNF)-alpha. These results suggest that enprostil affects a point in the pathway between the IL-1 receptor or LPS receptor and nuclear factor-kappa B(NF-kappa B), without affecting the pathway between the TNF receptor and NF-kappa B, with the latter factor being required for the IL-8 gene transcription. The therapeutic effect of exogenous enprostil on DSS colitis may involve the inhibition of IL-8 production in colonic epithelial cells stimulated by IL-1 beta or LPS.
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PMID:Enprostil, a prostaglandin-E(2) analogue, inhibits interleukin-8 production of human colonic epithelial cell lines. 1111 62

Interleukin (IL)-18 plays an important role in enhancing cellular immunity against cancer and bacteria. We constructed retroviral and adenoviral vectors that show improved secretion of bioactive murine IL-18 that could further enhance antitumor immunity in a murine model. Secretion of bioactive IL-18 was facilitated by fusing the leader sequences of prepro-parathyroid hormone (PTH) or IL-1 receptor antagonist (IL-1ra) to the 5; end of the mature murine IL-18 cDNA. Transfectants established by the retroviral vector carrying IL-1ra/IL-18 hybrid showed about 100-fold more IL-18 production and interferon (IFN)-gamma induction from splenocytes when compared with those carrying PTH/IL-18 hybrid. Repeated intraperitoneal injection of an adenoviral vector with IL-1ra/IL-18 hybrid ligated to IL-18 (Ad.IL-1ra.IL-18) successfully prevented establishment of human colon cancer cells in the abdominal cavity of mice. Treatment with Ad.IL-1ra.IL-18 was associated with significantly elevated levels of serum IL-18 and IFN- gamma. IL-18 administration also enhanced the cytostatic activity of peritoneal exudate cells against cancer cells. These improved viral vectors, which efficiently produce bioactive IL-18, could be used as a useful tool for cancer gene therapy.
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PMID:Construction and analysis of new vector systems with improved interleukin-18 secretion in a xenogeneic human tumor model. 1204 49

KITENIN promotes invasion of mouse colon adenocarcinoma (CT-26) cells in vivo. Here, we studied the effects of in vivo KITENIN ablation on established tumors by using pSUPER vectors (pSUPER-KITENIN) producing short interfering RNA (siRNA). When pSUPER-KITENIN was given weekly or semiweekly for 1 month into tail vein of syngeneic mice that have established colon tumors, tumor size regressed markedly and metastases were inhibited. In mice injected with pSUPER-KITENIN, serum interleukin-2 (IL-2) and IFN-gamma increased and CD4+ and CD8+ T cells infiltrated in the regressed tumor tissues. These effects, observed beginning 2 days after i.v. injection, imply that immune response is involved in the antitumor action of pSUPER-KITENIN. Using a yeast two-hybrid assay, we identified two KITENIN-interacting proteins for the possible mediators of these actions: 90K protein, a known immune modulatory glycoprotein, and protein kinase C inhibitor (PKCI). 90K was increased in the culture medium from CT-26/antisense KITENIN/90K cells. Double culture of accessory cells with CT-26/antisense KITENIN/90K cells revealed increased secretion of IL-1 and IL-6. Overexpression of 90K in CT-26/antisense KITENIN cells further delayed tumor growth compared with that of CT-26/antisense KITENIN cells. Actin arrangement was distorted in CT-26/antisense KITENIN and CT-26/antisense PKCI cells, whereas overexpression of PKCI resulted in increased invasiveness to fibronectin. Thus, antitumor effects of KITENIN siRNA derives from both the generation of a tumor-specific immune response in vivo through increased 90K secretion from tumor cells and the suppression of tumor invasion in which PKCI is related to increased invasiveness. Moreover, siRNA targeting of KITENIN can function as a chemotherapeutic strategy against colon cancer.
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PMID:Suppression of progression and metastasis of established colon tumors in mice by intravenous delivery of short interfering RNA targeting KITENIN, a metastasis-enhancing protein. 1620 73


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