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

Costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are indispensable for T-cell activation. Recently, a paucity of these costimulatory molecules was reported in inflammatory cells in colon cancer, which may permit the immune evasion of the cancer. The present study uses immunohistochemistry to reveal the expression of these molecules in 43 cases of colorectal cancer tissue. B7-2 was expressed in mononuclear calls distributed along the invasive margin in 37 of 43 cases. B7-1 was positive in the same area in 22 cases. In contrast, the expression of B7-1/B7-2 was usually inconspicuous in the stroma within cancer. Most B7-1+ and B7-2+ cells were identified as macrophages because of the coexpression of CD68 antigen or acid phosphatase activity. CD4+ or CD8+ T cells were distributed in the same area and were in close contact to B7-1/B7-2+ cells. Both CD4+ and CD8+ T cells had a proliferative activity with a labeling index of Ki-67 of 1.5% and 2.5%, respectively. Conventional electron microscopy confirmed both the accumulation of macrophages along the invasive margin and the attachment of lymphocytes to them. Immunoelectron microscopy confirmed: (a) localization of B7-2/B7-1 along the cell membrane; (b) abundance of vacuoles and heterophagosomes (a finding indicative of phagocytosis of other cells) in the cytoplasm of these cells; and (c) direct cell-to-cell contact between these macrophages and lymphocytes. The present data, which suggest that an immune reaction occurs along the invasive margin of colorectal cancer, are in accordance with previous clinicopathologic studies suggesting that peritumoral lymphocytic infiltration is one of the favorable prognostic factors in this disease.
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PMID:Expression of costimulatory molecules B7-1 and B7-2 by macrophages along invasive margin of colon cancer: a possible antitumor immunity? 931 47

C1311 is a novel therapeutic agent with potent activity against experimental colorectal cancer that has been selected for entry into clinical trial. The compound has previously been shown to have DNA-binding properties and to inhibit the catalytic activity of topoisomerase II. In this study, cellular uptake and mechanisms by which C1311 interacts with DNA and exerts cytotoxic effects in intact colon carcinoma cells were investigated. The HT29 colon cancer cell line was chosen to follow cellular distribution of C1311 over a time course of 24 h at drug concentrations that just inhibited cell proliferation by 50% or 100%. Nuclear uptake of C1311 and co-localization with lysosomal or mitochondrial dyes was examined by fluorescence microscopy and effects on these cellular compartments were determined by measurement of acid phosphatase levels, rhodamine 123 release or DNA-binding behaviour. The strength and mode of DNA binding was established by thermal melting stabilization, direct titration and viscometric studies of host duplex length. The onset of apoptosis was followed using a TUNEL assay and DNA-fragmentation to determine a causal relationship of cell death. Growth inhibition of HT29 cells by C1311 was concomitant with rapid drug accumulation in nuclei and in this context we showed that the compound binds to duplex DNA by intercalation, with likely A/T sequence-preferential binding. Drug uptake was also seen in lysosomes, leading to lysosomal rupture and a marked increase of acid phosphatase activity 8 h after exposure to C1311 concentrations that effect total growth inhibition. Moreover, at these concentrations lysosomal swelling and breakdown preceded apoptosis, which was not evident up to 24 h after exposure to drug. Thus, the lysosomotropic effect of C1311 appears to be a novel feature of this anticancer agent. As it is unlikely that C1311-induced DNA damage alone would be sufficient for cytotoxic activity, lysosomal rupture may be a critical component for therapeutic efficacy.
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PMID:Cellular uptake, cytotoxicity and DNA-binding studies of the novel imidazoacridinone antineoplastic agent C1311. 1049 67

The relationship between antioxidant and anticancer properties of probiotic bacterium strain Lactobacillus plantarum AS1 (AS1) in colon cancer induced by 1,2-dimethylhydrazine (DMH) has been studied. In this study, an increased level of lipid peroxide (LPO) products and increased activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione-S transferase) and marker enzymes (alkaline phosphatase and acid phosphatase) in colon and plasma of cancer-bearing animals have been observed. AS1 was supplemented either before initiation or during initiation and selection/promotion phases of colon carcinogenesis and was found to be effective in altering lipid peroxidation and antioxidant enzyme activities and marker enzymes to a statistically significant level measured either in the colon and in the plasma. These alterations inclined towards normal in a time-dependent manner on AS1 supplementation. The mean tumor volume diameter and total number of tumors were found to be statistically decreased in AS1 pre- and post-treated rats. Furthermore, histopathological examination shows remarkable difference between control and treated groups. The in vitro antioxidant assay shows that AS1 has promising antioxidant property. These results demonstrate that AS1 strain can modulate the development of DMH-induced rat colon carcinogenesis through an antioxidant-dependent mechanism.
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PMID:Lactobacillus plantarum AS1 isolated from south Indian fermented food Kallappam suppress 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in male Wistar rats. 2216 Dec 38

Colon cancer is a devastating illness that is associated with gut inflammation. Here, we explored the possible role of lipin-1, a phosphatidic acid phosphatase, in the development of colitis-associated tumorigenesis. Azoxymethane and dextran sodium sulfate-treated (DSS-treated) animals deficient in lipin-1 harbored fewer tumors and carcinomas than WT animals due to decreased cellular proliferation, lower expression of antiapoptotic and protumorigenic factors, and a reduced infiltration of macrophages in colon tumors. They also displayed increased resistance to DSS-induced colitis by producing less proinflammatory cytokines and experiencing less immune infiltration. Lipin-1-deficient macrophages from the colon were less activated and displayed lower phosphatidic acid phosphatase activity than WT macrophages isolated from DSS-treated animals. Transference of WT macrophages into lipin-1-deficient animals was sufficient to increase colitis burden. Furthermore, treatment of lipin-1-deficient mice with IL-23 exacerbated colon inflammation. Analysis of human databases from colon cancer and ulcerative colitis patients showed that lipin-1 expression is increased in those disorders and correlates with the expression of the proinflammatory markers CXCL1 and CXCL2. And finally, clinically, LPIN1 expression had prognostic value in inflammatory and stem-cell subtypes of colon cancers. Collectively, these data demonstrate that lipin-1 is a critical regulator of intestinal inflammation and inflammation-driven colon cancer development.
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PMID:The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis. 3023 75