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)

Epstein-Barr Virus-transformed B lymphoblastoid cell lines (EBV-LCLs) are routinely used for the in vitro expansion of T cells. However, these cell lines are reported to produce the cytokine IL-10, which is inhibitory for T cells. We, therefore, characterized a panel of 37 EBV-LCLs for a variety of cell surface markers, for secretion of various cytokines including IL-10 and for immunoglobulin production. These cell lines were derived from normal donors or patients with nonsmall cell lung cancer, acute myelogenous leukemia, melanoma or colon cancer. Overall, 26 lines were positive for CD19 and CD20, and 11 were negative for both. All of the lines were strongly HLA-DR+, while CD40 expression was variable. Twenty-four (65%) were both CD23+ and secreted immunoglobulin, and 33 expressed kappa and/or lambda light chains. Additionally, all of the EBV-LCLs were negative for T cell (CD3), NK cell (CD16, CD56), monocyte (CD14) and granulocyte (CD66b) surface markers. Some level of IL-10, IL-6, IL-12p40 and TNF-alpha cytokine production was detected in 33, 18, 19 and 12 EBV-LCLs, respectively. Together, these data reflect the heterogeneity of EBV-LCLs, which cautions their use nondiscriminately in various immunologic assays.
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PMID:Cell surface phenotyping and cytokine production of Epstein-Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCLs). 1219 5

Roles for host immune response in carcinogenesis are not well defined. Recent studies have shown that microbially driven inflammation can lead to colon cancer and that prior transfer of regulatory lymphocytes expressing CD4 and CD25 prevents the innate inflammatory events that lead to colon cancer in mice. To further examine the ability of regulatory lymphocytes to inhibit carcinogenesis, 129/SvEv Rag-2-deficient mice were inoculated by gastric gavage with Helicobacter hepaticus, an enteric bacterial pathogen of mice. Mice were then treated at 1, 3, or 12 months after infection with adoptive transfer of CD4(+)CD45RB(lo)CD25(+)-regulatory cells. Mice dosed with regulatory cells at 4 or 12 weeks after H. hepaticus infection had reduced severity of inflammatory bowel disease and significantly lower risk of colon cancer during the 8 month observation period, compared with infected mice that had not received cells. This suggested that regulatory cells were able to interrupt the ongoing innate immune events in the stepwise progression to cancer. Transfer of regulatory cells into chronically infected mice with established cancer reduced severity of colitis, epithelial dysplasia, and cancer, but did not eliminate all tumors. Regulatory cells lacking anti-inflammatory cytokine interleukin (IL)-10 were unable to inhibit inflammatory bowel disease, dysplasia, or cancer, showing that IL-10 was required for the protective effects of lymphocytes in this setting. Taken together, the data suggest that IL-10-mediated suppression of host innate inflammatory response was pivotal in interrupting carcinogenesis. Regulatory lymphocytes and cytokines may have implications for novel therapies for colon cancer in humans.
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PMID:CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. 1452 33

The immunosuppressive cytokine IL-10 is associated with poor prognosis in colon cancer. Although macrophages are involved in antitumor defenses, production of IL-10 by tumor cells may permit malignant cells escape to cell-mediated immune defenses. To investigate interactions between macrophages and tumor cells in humans, we cultured macrophages isolated from patients and tested the effect of these macrophages on the production of IL-10 by several tumor cell lines. Macrophages were isolated from pleural effusions of patients with malignancy and from noncancer control patients. We demonstrated that culture supernatants of macrophages from both sources strongly stimulated IL-10 production by the three different human colon adenocarcinoma cell lines, Colo 205, Colo 320, and HT29. Recombinant IL-6, but not IL-10, TNF-alpha, and IFN-alpha, stimulated the secretion of IL-10 by colon tumor cells. mAbs against IL-6 and IL-6R prevented the effect of macrophage culture supernatants and of rIL-6, respectively, on the production of IL-10 by the three cell lines. Cocultures of macrophages and colon cancer cells showed that these tumor cells first stimulated macrophages to produce IL-6, which was then followed by IL-6-induced IL-10 production by colon cancer cells. Finally, we showed that IL-10 gene regulation was mediated by STAT3, which was phosphorylated after the binding of IL-6 to IL-6R. This is the first demonstration that IL-6, secreted by macrophages, can induce a STAT3-mediated IL-10 production by colon tumor cells.
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PMID:Recruitment of STAT3 for production of IL-10 by colon carcinoma cells induced by macrophage-derived IL-6. 1503 82

IL-24/MDA-7 is a new member of the IL-10 family of cytokines, which signals through two heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2). Previously, we identified a rat gene named mob-5, which encodes a secreted protein that shares a high degree of homology with human IL-24. Expression of mob-5 and its putative cell surface receptors was shown to be upregulated by oncogenic ras. Here we show that not only do rat mob-5 and human IL-24 share a strikingly similar genomic structure but also that the rat MOB-5 protein can bind to and signal through the human IL-24 receptors. Like human IL-24, binding of the rat MOB-5 protein to the human IL-24 receptors leads to activation of the JAK/STAT pathway, which in turn supports receptor-dependent survival and proliferation of Ba/F3 cells. Furthermore, using human colon cancer cell lines with somatic knockout of either the mutant or the wild-type k-ras allele, we demonstrate that the human IL-24 receptors also are upregulated by oncogenic ras. Taken together, these results provide strong experimental evidence that MOB-5 is indeed the rat homolog of human IL-24.
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PMID:Conservation of the genomic structure and receptor-mediated signaling between human and rat IL-24. 1517 45

Probiotics (PRO) are known to modulate immunity in animals and human subjects and to inhibit colon carcinogenesis in experimental models, but the effects of synbiotics (SYN) are not well understood. Therefore, the effects of PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin-based enriched with oligofructose, 100 g/kg) and SYN (combination of PRO and PRE) on the immune system of rats were investigated in the azoxymethane (AOM)-induced colon cancer model. After 33 weeks, rats with and without AOM treatment were killed and immune cells were isolated from spleen, mesenterial lymph nodes (MLN) and Peyer's patches (PP). AOM treatment significantly reduced natural killer (NK) cell-like cytotoxicity in control rats and in PRO- and PRE-supplemented rats. SYN supplementation prevented the AOM-induced suppression of NK cell-like cytotoxicity in PP compared with control rats (P<0.01). SYN and PRE supplementation stimulated IL-10 production in PP in these rats (P<0.01) and in MLN of rats not treated with AOM (P<0.05). Interferon-gamma production in PP was decreased by PRO supplementation (PRO and SYN groups combined; P<0.05). Proliferative responsiveness of lymphocytes (PP) from AOM-treated rats was suppressed in SYN-supplemented rats (P<0.01). Overall, SYN supplementation in carcinogen-treated rats primarily modulated immune functions in the PP, coinciding with a reduced number of colon tumours. PRE and PRO provided in combination as SYN may contribute to the suppression of colon carcinogenesis by modulating the gut-associated lymphoid tissue.
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PMID:Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis. 1561 55

The transcription factor NF-kappa B is constitutively activated in many human cancers, and induces the expression of multiple proteins including antiapoptotic proteins. Recent papers indicate that NF-kappa B activation is inhibited by interleukin (IL)-10. In this study, we investigated the effect of IL-10 plasmid DNA on colon cancer in mice. In vitro study: Colon 26 murine colon adenocarcinoma cells were either treated or untreated with IL-10 for 60 min. The cells were subsequently stimulated with TNF-alpha. In vivo study: to induce a high level of IL-10 in plasma, we transferred the naked plasmid vectors encoding the mouse IL-10 gene into the liver via the intravenous route. To establish tumors, we injected Colon 26 cells into BALB/c mice subcutaneously. In vitro study: a 24-h incubation with TNF-alpha did not affect cell viabilities; however, pretreatment with IL-10 significantly enhanced the level of apoptosis induced by TNF-alpha. Pretreating Colon 26 cells with IL-10 significantly attenuated the TNF-alpha-induced NF-kappa B activation. In vivo study: IL-10 plasmid controlled the growth of subcutaneous tumors. In subcutaneous tumor, NF-kappa B was activated in response to tumor growth. IL-10 plasmid markedly inhibited this activation of NF-kappa B in subcutaneous tumor. IL-10 plasmid induced cancer cell apoptosis linked to the down-regulation of antiapoptotic proteins, and the activation of caspase-3. These results demonstrate that IL-10 plasmid may constitute a new strategy for treating cancer growth.
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PMID:Interleukin-10 plasmid DNA inhibits subcutaneous tumor growth of Colon 26 adenocarcinoma in mice. 1567 Aug 94

Diet is known to modulate immune functions in multiple ways and to affect host resistance to infections. Besides the essential nutrients, non-essential food constituents such as non-digestible carbohydrates may also have an impact on the immune system, especially in the area of the gut-associated lymphoid tissue (GALT). Recent data now provide first evidence that prebiotics such as inulin/oligofructose (IN/OF) modulate functions of the immune system. In animal studies IN/OF primarily activated immune cells in Peyer's patches including IL-10 production and natural killer (NK) cell cytotoxicity. Other immune functions modulated by IN/OF included the concentration of secretory IgA in ileum and caecum, splenic NK cell cytotoxicity as well as splenocyte cytokine production. In different tumour models, a lower incidence of tumours was observed, which in the case of colonic tumours was associated with enhanced NK cell cytotoxicity in the GALT. Few human studies so far have investigated the effects of IN/OF alone or in combination with other dietary supplements on immunocompetence. Supplementation of IN/OF resulted in minor changes of systemic immune functions such as decrease in phagocytic activity. No data are available on the effects of IN/OF on the GALT in man. The mechanisms of the reported effects of IN/OF on the immune system are currently investigated and include: (i) direct effects of lactic acid-producing bacteria or bacterial constituents on immune cells; (ii) the production of SCFA and binding to SCFA receptors on leucocytes. In conclusion, the current data suggest that IN/OF primarily modulate immune parameters in the GALT, but splenocytes are also activated by IN/OF. Human studies are needed to find out whether IN/OF have the potential to modulate systemic immunity in well-nourished individuals and to lower the risk of diseases such as colon cancer.
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PMID:Inulin, oligofructose and immunomodulation. 1587 95

Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone 'curative resection' and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 x 10(10) colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 x 10(10) colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-beta1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0.05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-gamma at T3 (P < 0.05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system.
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PMID:Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients. 1734 80

The idea of generating cytotoxic T-lymphocytes that have anti-tumor activity has been the focus of many clinical trials aimed at delivering effective immunotherapy to cancer patients. We have gained insight into the human immune system in cancer patients as a result of these numerous clinical investigations. It is now clear that although various vaccination methods are capable of inducing tumor antigen-specific T-cells in the circulating blood, these immunological responses are infrequently correlated with clinical responses. Therefore, it appears that priming of a T-cell response is not sufficient for tumor regression and other avenues, downstream of the priming phase, need to be investigated. Mechanisms of immune evasion at the effector phase of the anti-tumor phase are currently under investigation, with an increasing focus on the tumor microenvironment. There is evidence indicating that multiple variables may contribute to immune escape, including: regulatory cells; inhibitory ligands on tumor cells, such as PD-L1 and B7x; soluble factors such as TGF-beta and IL-10; and nutrient-catabolizing enzymes, such as indoleamine-2,3-dioxygenase (IDO). In addition, there are ongoing efforts to assess the presence and function of effector cells within the tumor microenvironment. Tumor infiltrating lymphocytes (TILs) have been observed in patients with melanoma, colon cancer, and ovarian cancer. TILs in these patients have been associated with favorable clinical outcomes. In the clinical setting of bladder cancer, as compared to melanoma, there is limited data regarding TILs. This review will focus on immunological responses to bladder cancer and ongoing studies to identify factors that are amenable to therapeutic manipulation.
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PMID:Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human bladder cancer. 1759 43

Epithelial cell MUC1 is aberrantly expressed on human epithelial adenocarcinomas where it functions as a regulator of immune responses and an oncogene. Normally expressed at low levels in healthy colonic epithelium, MUC1 was reported to be overexpressed in human inflammatory bowel disease (IBD) and thus may be expected to play an important role in regulating chronic inflammation and its progression to colitis-associated colon cancer. Studies in the immunobiology and pathology of IBD and colitis-associated colon cancer have been done in various mouse models but none could properly address the role of MUC1 due to low homology between the mouse and the human molecule. We report that IL-10(-/-) mice, a widely accepted mouse model of IBD, crossed to human MUC1-transgenic mice, develop MUC1(+) IBD characterized by an earlier age of onset, higher inflammation scores, and a much higher incidence and number of colon cancers compared with IL-10(-/-) mice.
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PMID:Cutting edge: transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer. 1761 60

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