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)

Connections among specific proteins (Bax, Bcl-2, bFGF, COX-1, COX-2, E-cad, p15, p53, PCNA, TGFbeta3, TUNEL, vWF) in control of cell proliferation, apoptosis, cell adhesion, tumor vascularity and PGE2 content were evaluated in colon cancer as related to disease progression and survival. Tumor tissue and adjacent normal colon mucosa were obtained at curative resection in 22 patients. PGE2 concentrations were assessed in tumor tissue and tumor derived blood, splanchnic blood, peripheral venous blood and urine. Host inflammation was determined (CRP, ESR) in relationship to tumor differentiation and stage. Patients survived as expected according to Dukes A-D staging. Growth-related proteins correlated between tumor cells and stroma as well as between protein factors within tumor cells and tumor stroma. COX-2 predicted tumor tissue content of PGE2 (p<0.002), without reflection in tumor derived blood. Systemic inflammation was predicted by p15, TGFbeta3 and Bcl-2 in tumor tissue (p<0.001). p15 and vWF predicted reduced survival in ungrouped patients (p<0.02), while p15, PCNA, TGFbeta3 and vWF predicted reduced survival (p<0.0001) when patient grouping accounted for high tumor content of PGE2. Our results connect systemic inflammation and survival to COX-2 staining and increased PGE2 in colon cancer. Thus, it seems important to understand proximal signals behind upregulation of COX-2 and subsequent PGE2 production in certain tumor cells in colon cancer.
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PMID:Growth associated proteins in tumor cells and stroma related to disease progression of colon cancer accounting for tumor tissue PGE2 content. 1836 Jul 18

Propionibacterium freudenreichii, a food-grade bacterium able to kill colon cancer cell lines in vitro by apoptosis, may exert an anticarcinogenic effect in vivo. To assess this hypothesis, we administered daily 2 x 10(10) colony-forming units (CFU) of P. freudenreichii TL133 to human microbiota-associated (HMA) rats for 18 d. Either saline or 1,2-dimethylhydrazine (DMH) was also administered on days 13 and 17 and rats were killed on day 19. The levels of apoptosis and proliferation in the mid and distal colon were assessed by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunolabelling, respectively. The administration of P. freudenreichii TL133 significantly increased the number of apoptotic cells in DMH-treated rats compared to those given DMH only (P < 0.01). Furthermore, propionibacteria were able to decrease the proliferation index in the distal colon after treatment with DMH (P < 0.01). Conversely, propionibacteria alone did not exert such an effect on healthy colonic mucosa. P. freudenreichii TL133 thus facilitated the elimination of damaged cells by apoptosis in the rat colon after genotoxic insult and may play a protective role against colon cancer.
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PMID:Increased induction of apoptosis by Propionibacterium freudenreichii TL133 in colonic mucosal crypts of human microbiota-associated rats treated with 1,2-dimethylhydrazine. 1846 53

Low folate intake is associated with colon cancer. We combined a proteomics and biochemical approach to identify proteins and pathways affected by folate deficiency in human colonocytes. Folate differentially altered activity and expression of proteins involved in proliferation [e.g., PCNA], DNA repair [e.g., XRCC5, MSH2], apoptosis [e.g., BAG family chaperone protein, DIABLO and porin], cytoskeletal organization [e.g., actin, ezrin, elfin], and expression of proteins implicated in malignant transformation [COMT, Nit2].
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PMID:The response of human colonocytes to folate deficiency in vitro: functional and proteomic analyses. 1859 13

The mushroom Agaricus blazei (Ab) has been widely used in folk medicine to treat various diseases including cancer. No information is available on its possible protective effects on the development of colon cancer. The potential blocking effect of Ab intake on the initiation stage of colon carcinogenesis was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. Male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg bw, twice a week), during 2 weeks to induce ACF. The diet containing Ab at 5% was given 2 weeks before and during carcinogen treatment to investigate the potential beneficial effects of this edible mushroom on DMH-induced ACF. All groups were killed at the end of the fourth week. The colons were analyzed for ACF formation in 1% methylene blue whole-mount preparations and for cell proliferation in histological sections immunohistochemically stained for the proliferating cell nuclear antigen (PCNA). All DMH-treated rats developed ACF mainly in the middle and distal colon. Agaricus blazei intake at 5% did not alter the number of ACF induced by DMH or the PCNA indices in the colonic mucosa. Thus, the results of the present study did not confirm a chemopreventive activity of Ab on the initiation stage of rat colon carcinogenesis.
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PMID:Lack of chemoprevention of dietary Agaricus blazei against rat colonic aberrant crypt foci. 1878 4

Although aging is associated with increased proliferation and decreased apoptosis in the colonic mucosa of Fischer 344 rats, the regulatory mechanisms are poorly understood. Gene expression profiling (Illumina platform) was carried out in freshly isolated colonic mucosal cells from young (4-6 mo old) and aged (22-24 mo old) Fischer 344 rats. Sixty-six genes were differentially expressed in the colonic mucosa between young and old animals (P<0.05). In particular, the expression of schlafen 3, a negative regulator of proliferation, was decreased by 8- to 10-fold in the colonic mucosa of aged rats. Administration of wortmannin, which inhibited colonic mucosal proliferation in the colonic mucosa of aged rats, stimulated the expression of schlafen 3, indicating a growth regulatory role of this gene. To further determine the growth regulatory properties of schlafen 3 gene, schlafen 3 cDNA was transfected in colon cancer HCT-116 cells. This resulted in a 30-40% inhibition of cellular growth, accompanied by decreased expression of PCNA and cyclin D1 and reduced phosphorylation of retinoblastoma protein. In conclusion, our present study demonstrates that several genes involved in proliferation and apoptosis are differentially expressed in the colonic mucosa of young and aged rats. Schlafen 3, a novel negative regulator of growth, which is markedly downregulated in the colonic mucosa of the aged, may play a role in regulating colonic mucosal growth during aging.
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PMID:Schlafen 3, a novel gene, regulates colonic mucosal growth during aging. 1922 83

The present study investigated the role of calcineurin (CaN) in the proliferation of human colorectal cancers. CaN activity and protein expression were increased in human colorectal cancers. Nuclear transcription factor NFAT, a physiological substrate for CaN, was activated in human colon cancer specimen as well as in the human colon cancer cell lines. CaN inhibitor cyclosporine A (CsA) reduced cell growth in these cell lines. CsA decreased the expressions of c-Myc and the proliferating cell nuclear antigen (PCNA) but also increased p21(WAF1/CIP1) expression. Our results suggest that CaN promotes colorectal cancer proliferation probably by regulating levels of c-Myc, p21(WAF1/CIP1), and PCNA.
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PMID:Cyclosporine A inhibits colorectal cancer proliferation probably by regulating expression levels of c-Myc, p21(WAF1/CIP1) and proliferating cell nuclear antigen. 1948 39

We previously identified the induction of senescence in melanoma cell lines sensitive to diterpene esters, indicating a therapeutic potential. Here we compared the cytostatic effects of two diterpene esters: the prototypic PKC-activating drug TPA (12-O-tetradecanoylphorbol-13-acetate), and the novel compound PEP008 (20-O-acetyl-ingenol-3-angelate) in cell lines derived from melanoma, breast cancer and colon cancer. The diterpene esters induced permanent growth arrest with characteristics of senescence in a subset of cell lines in all three solid tumor models at 100-1000 ng/ml. Use of the PKC inhibitor bisindolylmaleimide-l demonstrated that activation of PKC was required for growth arrest. Full genome expression profiling identified pivotal genes involved in DNA synthesis and cell cycle control down-regulated by treatment in all three sensitive tumor models. At the protein level, prolonged down-regulation of E2F-1 and proliferating cell nuclear antigen (PCNA), sustained expression of p21(WAF1/CIP1) and dephosphorylation of retinoblastoma (Rb) occurred in the sensitive cells. Additionally, the type II tumor suppressor HRASLS3, which has a role in mitogen-activated protein kinase (MAPK) pathway suppression, was constitutively elevated in cell lines resistant to the senescence effects compared to their sensitive counterparts. Together, these results demonstrate that both TPA and the novel PKC-activating drug PEP008 induce growth arrest with characteristics of senescence in solid tumor cell lines derived from a variety of tissue types, and by a similar mechanism. PKC-activating diterpene esters may therefore have therapeutic potential in a subset of breast cancer, colon cancer and melanoma tumors.
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PMID:The induction of senescence-like growth arrest by protein kinase C-activating diterpene esters in solid tumor cells. 1963 13

Our previous studies and those of others have indicated that X-linked inhibitor of apoptosis protein (XIAP) holds promise as a target gene in colon cancer gene therapy. In this study, we constructed an adenoviral vector to deliver small hairpin RNA (shRNA) against XIAP (XIAP-shRNA) into colon cancer cells and tested its therapeutic efficacy in vitro and in vivo. We first confirmed an overexpression of XIAP in colon cancer cells and human cancer tissues. We then designed XIAP-small interfering RNA (siRNA) and confirmed the knockdown effect of these siRNAs in colon cancer cells. The sequences of the effective siRNAs were converted into shRNA and then packed into replication-deficient adenoviral vectors using BLOCK-iT Adenoviral RNAi Expression System to generate Adv-XIAP-shRNA. Infection of HT29 and HCT116 cells with Adv-XIAP-shRNA led to enhanced caspase-3 activity, which was associated with increased apoptosis and reduced cell proliferation. The therapeutic effect of Adv-XIAP-shRNA was then tested in xenograft tumors in nude mice. We showed that treatment of the xenograft tumors derived from HCT116 cells with Adv-XIAP-shRNA resulted in a retardation of tumor growth, which was associated with enhanced apoptosis, increased caspase-3 activity, and reduced expression of proliferating cell nuclear antigen in the tumor tissues. Treatment of xenograft tumors with Adv-XIAP-shRNA did not affect the expressions of inflammatory cytokines in tumor-bearing mice. Thus, Adv-XIAP-shRNA-mediated down-regulation of XIAP exerts a therapeutic effect in colon cancer by promoting apoptosis and inhibiting proliferation of colon cancer cells, and the antitumor effect of Adv-XIAP-shRNA was unlikely to be related to virus-induced immune response.
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PMID:Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer. 1973 40

Exosomes are 40-100-nm-diameter nanovesicles of endocytic origin that are released from diverse cell types. To better understand the biological role of exosomes and to avoid confounding data arising from proteinaceous contaminants, it is important to work with highly purified material. Here, we describe an immunoaffinity capture method using the colon epithelial cell-specific A33 antibody to purify colorectal cancer cell (LIM1215)-derived exosomes. LC-MS/MS revealed 394 unique exosomal proteins of which 112 proteins (28%) contained signal peptides and a significant enrichment of proteins containing coiled coil, RAS, and MIRO domains. A comparative protein profiling analysis of LIM1215-, murine mast cell-, and human urine-derived exosomes revealed a subset of proteins common to all exosomes such as endosomal sorting complex required for transport (ESCRT) proteins, tetraspanins, signaling, trafficking, and cytoskeletal proteins. A conspicuous finding of this comparative analysis was the presence of host cell-specific (LIM1215 exosome) proteins such as A33, cadherin-17, carcinoembryonic antigen, epithelial cell surface antigen (EpCAM), proliferating cell nuclear antigen, epidermal growth factor receptor, mucin 13, misshapen-like kinase 1, keratin 18, mitogen-activated protein kinase 4, claudins (1, 3, and 7), centrosomal protein 55 kDa, and ephrin-B1 and -B2. Furthermore, we report the presence of the enzyme phospholipid scramblase implicated in transbilayer lipid distribution membrane remodeling. The LIM1215-specific exosomal proteins identified in this study may provide insights into colon cancer biology and potential diagnostic biomarkers.
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PMID:Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. 1983 82

The chemopreventive effects of curcumin and green tea catechins individually and in combination on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis were studied in male Wister rats following 32 weeks of dietary treatment. The incidence, number and size of colorectal cancer were measured. Colorectal aberrant crypt foci (ACF) were analyzed by methylene blue staining. Proliferation indices and apoptotic indices were determined by PCNA immunostaining and TUNEL assay, respectively. The results showed that dietary curcumin, catechins and combination administration significantly inhibited the total number of ACF per rat. The combination treatment displayed the most potent inhibitory effect, while there was no difference of inhibition between curcumin and catechins-treated groups. The incidence of colorectal cancer in the treated groups was significantly lower than that of positive control group. Compared with the positive control group, the proliferation index was significantly decreased and the apoptotic index was significantly increased in all treatment groups, while the effect of the combination was the greatest among the treated groups. Our findings suggest that the combination of curcumin and catechins may produce a synergistic colon cancer-preventative effect that would be more potent than each of the compounds alone.
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PMID:Combination of curcumin and green tea catechins prevents dimethylhydrazine-induced colon carcinogenesis. 1986 Nov 45


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