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)

Activation of C-Ki-ras oncogene by point mutation within codon 12,13 was determined by Polymerase Chain Reaction (PCR) using specific oligonucleotide probes. In 9 of 42 colon cancer specimens point mutations in codon 12 of C-Ki-ras oncogene were found. The point mutations identified were GGT(Gly)----GAT(Asp) (4 cases), GGT (Gly)----TGT (Cys) (3 cases) and GGT(Gly)----GTT(Val) (2 cases), respectively. Two types of point mutations (GGT----GAT, GGT----TGT) were found simultaneously in one specimen. The results showed that there was no relationship between the point mutation of C-Ki-ras oncogene and patient's sex, age, state of metastasis or prognosis.
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PMID:[Detection of point mutations of C-Ki-ras oncogene in colon cancer by PCR using specific oligonucleotide probes]. 139 73

The inducing effect of transforming growth factor-beta (TGF-B) on carcinoembryonic antigen (CEA) secretion and the cellular expression of CEA and CEA crossreactive glycoproteins (CEA-GLY) was examined from a panel of human colonic cell lines with different phenotypic classification. This panel included carcinomas with dissimilar differentiation characteristics and metastatic behavior, and premalignant adenomas derived from colonic polyps. A great degree of heterogeneity was observed in the endogenous levels of CEA secretion and the cellular expression of CEA and CEA-GLY species. The response profiles of the different cell lines to TGF-B treatment were also found to be heterogenous. However, TGF-B was able to induce CEA secretion and up-modulated the cellular expression of CEA and CEA-GLY from a majority of the cells tested. More importantly, TGF-B was able to exert these effects on carcinoma cells that secrete or express minimal or nondetectable amounts of these glycoproteins. These biologic modifying effects of TGF-B may have potential in augmenting the efficacy of CEA as a colon cancer marker, and in antibody-directed radioimaging and therapeutics. Further investigation in vivo in an experimental animal model system is warranted.
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PMID:Induction of carcinoembryonic antigen and its crossreactive gene products in human colonic adenomas and carcinomas by transforming growth factor-beta. 233 36

Laminin, a major basement membrane-specific glycoprotein, promotes the attachment, migration, and invasion of a variety of tumor cells. Since laminin is present in the perisinusoidal matrix of the liver, we studied its effects on liver colonization by human colon cancer cells (HM7, LiM6) previously shown to have liver-metastasizing ability in athymic mice. These malignant cells expressed high levels of a 32-kDa laminin-binding protein on Western blot analysis when compared to the low metastatic parental cell line. Coinjection of laminin alpha chain-derived peptides which contain the amino acid sequence Ile-Lys-Val-Ala-Val (IKVAV) significantly stimulated liver colonization as determined by liver weight (P < 0.005) and number of tumor nodules (P < 0.02) 3 weeks after splenic-portal inoculation into nude mice. No stimulation was seen with a control peptide containing the same amino acids but in a scrambled sequence. In contrast, the Tyr-Ile-Gly-Ser-Arg peptide from the laminin beta 1 chain significantly inhibited HM7 liver colonization. These differences were not due to alterations in the number of cells initially reaching the liver as determined by injection of [125I]iododeoxyuridine-labeled tumor cells, but retention in the liver was stimulated by the IKVAV-containing peptides. Flow analysis indicated that the IKVAV peptide may act, in part, by stimulating homotypic adhesion of tumor cells. These data suggest that interactions of colon cancer cells with the IKVAV site on laminin may play a role in the formation of metastatic foci in the liver through cell-cell or cell-substratum interactions which promote metastasis.
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PMID:The laminin alpha 1 chain Ile-Lys-Val-Ala-Val (IKVAV)-containing peptide promotes liver colonization by human colon cancer cells. 775 2

KRN 5500 is a new semi-synthetic antitumor compound derived from spicamycin and has a unique structure. The compound showed a broad spectrum of antitumor activity against human colon, stomach, esophageal, breast and lung cancer xenografts in nude mice. Therapeutic efficacy of KRN 5500 against liver metastasis of COL-1 human colon cancer scid mice was examined. The treatment with KRN 5500 inhibited tumor growth in the liver and reduced the serum TPA concentration to a normal level. KRN 5500 inhibits protein synthesis in rabbit reticulocyte lysates. Among several metabolites of KRN 5500, only SAN-Gly showed a potent inhibitory activity against protein synthesis in reticulocyte lysates. TLC analysis of KRN 5500 metabolites using 7 human colon cancer cell lines and 3 normal cell lines demonstrated a correlation between the cytotoxicity of KRN 5500 and converting activity from KRN 5500 to SAN-Gly. These results indicate that SAN-Gly is the intracellular active metabolite and that converting activity from KRN 5500 to SAN-Gly is the major determinant of KRN 5500 cytotoxicity.
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PMID:[Protein synthesis inhibitor--antitumor activity and mode of action of KRN 5500]. 930 56

The human colon adenocarcinoma cell lines Colo 201 and Colo 205 lose adhevise capacity to the extracellular matrix (ECM) and take on a round and floating cell shape. Treatment of these cells with all-trans-retinoic acid (RA) results in inhibition of growth and in a marked increase in the production of carcinoembryonic antigen, thereby indicating that the cells undergo differentiation. This RA-induced differentiation was accompanied by a large increase in the degree of cell adhesion with localization of E-cadherin molecules at cell-cell contact sites. We examined several adhesion molecules involved in cell-cell and cell-ECM interaction by immunoblotting, but no change in E-cadherin, intercellular adhesion molecule-1, or CD44 was observed in RA-treated Colo 201 cells. Although the adhesion of Colo 201 cells to ECM depends on the Arg-Gly-Asp sequence, levels of integrins, alpha 2, alpha 3, alpha 5, alpha V, and beta 1 in differentiated adherent cells were similar to those in untreated cells. In contrast to equivalent amounts of cell surface adhesion molecules before and after differentiation, intracellular focal adhesion kinase (FAK) was markedly induced during RA treatment, and the increase in FAK resulted in elevation of tyrosine-phosphorylated FAK. These findings suggest a role for FAK in activation of cell adhesion of RA-induced differentiation of these colon cancer cells. This may serve as an appropriate model to examine the mode of activation of the adhesive capacity of cancer cells.
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PMID:Acquisition of cell adhesion and induction of focal adhesion kinase of human colon cancer Colo 201 cells by retinoic acid-induced differentiation. 956 10

Although the frequency of activated Ki-ras genes is high in human colorectal tumors, much less is known of activated Ki-ras-mediated signaling pathways. Using gene targeting, we examined HCT116 cells that contain the Gly-13-->Asp mutation of Ki-ras and activated Ki-ras-disrupted clones derived from HCT116. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced immediate early genes, such as c-Jun, c-Fos, and Egr-1 in activated Ki-ras-disrupted clones, whereas c-Jun induction was rare in HCT116. TPA induced both phosphorylation of stress-activated protein kinase kinase 1 (SEK1) and c-Jun NH2-terminal kinase (JNK) in the activated Ki-ras-disrupted clones but not in HCT116. On the other hand, TPA-induced mitogen-activated protein kinase kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase (ERK) activation was equally induced between HCT116 and the Ki-ras-disrupted clones. Furthermore, TPA-induced SEK1-JNK activation was observed in a DLD-1-derived activated Ki-ras-disrupted clone but not in DLD-1. The TPA-induced SEK1-JNK activation in these disrupted clones was completely inhibited by the protein kinase C (PKC) inhibitor, GF109203X (1 microM), but not by another PKC inhibitor, H7 (50 microM), whereas TPA-induced MEK1/2-ERK activation was partially and completely inhibited by GF109203X (1 microM) and H7 (50 microM), respectively. A phosphoinositol 3-kinase inhibitor, LY294002, did not inhibit the TPA-induced SEK1-JNK activation. Taken together, these results suggest that activated Ki-Ras-mediated signals are involved in the SEK1-JNK pathway through a PKC isotype that is distinct from that involved in MEK1/2-ERK activation in human colon cancer cells and independent of phosphoinositol 3-kinase activation, and the imbalance between ERK and JNK activity caused by activated Ki-Ras may play critical roles in human colorectal tumorigenesis.
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PMID:Activated Ki-Ras suppresses 12-O-tetradecanoylphorbol-13-acetate-induced activation of the c-Jun NH2-terminal kinase pathway in human colon cancer cells. 1034 56

We performed dual (two-color) fluorescence in situ hybridization (FISH) using direct fluorescent labeling probes for p53 and chromosome 17 in six gastrointestinal (3 stomach and 3 colon) cancers. In three of these (1 stomach and 2 colon) the interphase cell nuclei showed an imbalance of signals for the p53 and chromosome 17; that is, the p53 signal count was lower than the chromosome 17 signal count, indicating deletion of the p53 gene. Moreover, metaphase FISH analysis demonstrated that those nuclei actually had a chromosome 17 with deletion of the p53 gene. Interestingly, these three cases had an abnormal chromosome 17 copy number, that is, chromosome 17 aneusomy. Furthermore, to investigate the possibility of p53 mutation in tumors with an imbalance of signals for chromosome 17 and p53 per nucleus, we performed a GeneChip p53 assay which has recently been developed. GeneChip p53 assay demonstrated that a primary tumor sample from one colon cancer case had a heterozygous point mutation of CGT (Arg) to CAT (His) at codon 273 in exon 8. In addition, a sample of metastatic tumor in the liver from the same case revealed two heterozygous point mutations. One of them was the same mutation as that is the primary tumor; the other was GTG (Val) to GGG (Gly) at codon 217 in exon 6. In conclusion, we found that the combination of dual-color FISH and GeneChip p53 assay offered reliable results and important information concerning not only deletion of the p53 gene and chromosome 17 aneusomy but also p53 mutations. Using these techniques, we demonstrated that an imbalance of signals for chromosome 17 and p53 per nucleus, chromosome 17 aneusomy, and accumulation of p53 mutations had occurred during carcinogenesis and development of gastrointestinal cancers.
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PMID:Detection of aberrations of 17p and p53 gene in gastrointestinal cancers by dual (two-color) fluorescence in situ hybridization and GeneChip p53 assay. 1095 39

Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin alpha(V)beta3 and acts as an angiogenic inhibitor. A novel cyclic RGD peptide, cyclo(-RGDf==V-) (f==V), was synthesized and its biological activities were characterized and compared with its analogs, cyclo(-RGDfV-) (fV) and cyclo(-RGDf-MeV-) (fMeV). It bound to integrin alpha(V)beta3 with almost the same affinity as the fV and fMeV analogs. All three compounds inhibited the adhesion and growth of HUVEC cells in a dose-dependent manner in vitro. Out of three, fMeV had the strongest effect, f==V was almost as strong as fMeV, and fV had the least effect. However, in vivo, f==V significantly decreased the intratumoral microvessel density (MVD) in the DLD-1 (human colon cancer cell) inoculated mice, while fMeV had little effect. These results suggest the potential usefulness of the cyclo(-RGDf==V-) as an antiangiogenic agent for clinical use in the future.
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PMID:A novel synthetic Arg-Gly-Asp-containing peptide cyclo(-RGDf==V-) is the potent inhibitor of angiogenesis. 1167 1

Expression analysis of genes encoding components of the phosphotyrosine signaling system by cDNA array hybridization revealed elevated levels of FGFR4 transcripts in several mammary carcinoma cell lines. In the FGFR4 gene transcript from MDA-MB-453 mammary carcinoma cells, a G to A conversion was discovered that results in the substitution of glycine by arginine at position 388 in the transmembrane domain of the receptor. The Arg(388) allele was also found in cell lines derived from a variety of other tumor types as well as in the germ-line of cancer patients and healthy individuals. Analysis of three geographically separated groups indicated that it occurs in approximately 50% of the human population. Investigation of the clinical data of 84 breast cancer patients revealed that homo- or heterozygous carriers of the Arg(388) allele had a significantly reduced disease-free survival time (P = 0.01) within a median follow-up of 62 months. Moreover, the FGFR4 Arg(388) allele was associated with early lymph node metastasis and advanced tumor-node-metastasis (TNM) stage in 82 colon cancer patients. Consistent with this finding, MDA-MB-231 mammary tumor cells expressing FGFR4 Arg(388) exhibited increased motility relative to cells expressing the FGFR4 Gly(388) isotype. Our results support the conclusion that the FGFR4 Arg(388) allele represents a determinant that is innocuous in healthy individuals but predisposes cancer patients for significantly accelerated disease progression.
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PMID:Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. 1183 May 41

Three amino acids residues, Arg-Gly-Asp (RGD), in vitronectin and fibronectin show affinity for alpha(V)beta(3) integrins expressed in vascular endothelial cells. That tumor growth can upregulate the expression of these integrins on tumor cells for invasion and metastasis and in tissue neovasculature suggests the potential of developing radiolabeled RGD peptides as antagonists of alpha(V)beta(3) integrins for broad spectrum tumor specific imaging. The polypeptide RGD-4C, which contains four cysteine residues for cyclization, has shown preferential localization on integrins at sites of tumor angiogenesis. Both RGD-4C and RGE (Arg-Gly-Glu)-4C (as control) were purchased and conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) for 99mTc radiolabeling. After purification of the conjugated peptides by a C18 Sep-Pak cartridge with 20% methanol, both peptides were radiolabeled using tricine. For cell binding studies, both 99mTc peptides were further purified by SE HPLC. High specific radioactivity of labeled cyclized RGD/E (cyclized RGD/E will be simplified as RGD/E through out the text) of about 20 Ci/micromol was achieved. Both 99mTc complexes were stable in the labeling solution for over 24 h at room temperature. In the human umbilical vein endothelial (HUVE) cell studies, the binding at 1 h of radiolabeled RGD/E was determined at 4 degrees C and at concentrations in the picomolar to nanomolar range. Under these conditions, cell accumulation of 99mTc in the case of RGD was as much as 16 times greater than the control RGE. As a check on specificity, 7 nM of native cyclized RGD blocked 50% of the binding of 99mTc-labeled RGD to cells. The binding percentage of 99mTc-labeled RGD to purified alpha(V)beta(3) integrin protein, as determined by SE HPLC, increased with the concentration of the integrin while 99mTc-labeled RGE showed no binding. The association constant for 99mTc-RGD was modest at 7 x 10(6) M(-)(1). In both human renal adenocarcinoma (ACHN) and human colon cancer cell line (LS174T) nude mouse tumor models, the accumulation of 99mTc-labeled RGD/E exhibited no statistical difference. In conclusion, possibly because of limited numbers of alpha(V)beta(3) integrin receptors per tumor cell and low binding affinity, radiolabeled RGD peptides may have limitations as tumor imaging agents.
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PMID:In vitro and in vivo evaluation of a Technetium-99m-labeled cyclic RGD peptide as a specific marker of alpha(V)beta(3) integrin for tumor imaging. 1264 34


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