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)

A more accurate method of detecting nodal disease in squamous cell carcinoma of the tongue is needed so that treatment of the neck with its associated morbidity can safely be reserved for patients who actually have metastatic disease. Tumor angiogenesis and the expression of the p53 antigen--which have each been shown to be predictive of metastasis in breast and colon cancer, respectively--are examined for their ability to predict neck metastasis in tongue cancer. Fifty-seven patients with T1 and T2 squamous cell carcinoma of the oral tongue, whose neck disease was examined by dissection or by 2-year follow-up, were studied. Twenty-eight patients (49%) were node positive and 29 patients (51%) were node negative. The primary tumors were immunohistochemically stained for the p53 antigen and for factor VIII, which allowed the blood vessels within the tumor to be quantitated. The mean vessel counts per x200 high-power field were 59.8 and 61.5 for node-positive and node-negative patients, respectively (p = 0.8). Node-positive patients showed overexpression of p53 43% of the time, vs. 61% for node-negative patients (p = 0.17). Multivariate analysis confirmed that no difference in tumor angiogenesis or the expression of the p53 antigen was found between tumors that had metastasized and those that had not. Therefore neither tumor angiogenesis nor the p53 tumor marker is clinically useful in determining lymph node metastasis in these patients.
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PMID:Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma of the tongue. 752 5

An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1 alpha,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 micrograms/kg body weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control. DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner over the range of 0.1-10 micrograms/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.
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PMID:Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003. 792 32

The growth and metastatic spread of cancer is directly related to tumor angiogenesis, and the driving factors need to be understood to exploit this process therapeutically. However, tumor cells and their normal stroma express a multitude of candidate angiogenic factors, and very few specific inhibitors have been generated to assess which of these gene products are only innocent bystanders and which contribute significantly to tumor angiogenesis and metastasis. Here we investigated whether the expression in tumors of a secreted fibroblast growth factor (FGF)-binding protein (FGF-BP) that mobilizes and activates locally stored FGFs (ref. 11) can serve as an angiogenic switch molecule. Developmental expression of the retinoid-regulated FGF-BP gene is prominent in the skin and intestine during the perinatal phase and is down-modulated in the adult. The gene is, however, upregulated in carcinogen-induced skin tumors, in squamous cell carcinoma (SCC) and in some colon cancer cell lines and tumor samples. To assess the significance of FGF-BP expression in tumors, we depleted human SCC (ME-180) and colon carcinoma (LS174T) cell lines of their endogenous FGF-BP by targeting with specific ribozymes. We found that the reduction of FGF-BP reduced the release of biologically active basic FGF (bFGF) from cells in culture. Furthermore, the growth and angiogenesis of xenograft tumors in mice was decreased in parallel with the reduction of FGF-BP. This suggests that human tumors can utilize FGF-BP as an angiogenic switch molecule.
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PMID:A secreted FGF-binding protein can serve as the angiogenic switch in human cancer. 933 15

Sialoglycans on the cell surface of human colon cancer (HCC) cells have been implicated in cellular adhesion and metastasis. To clarify the role of N-acetylneuraminic acid (NeuAc) linked alpha2,3 to galactose (Gal) on the surface of HCC cells, we studied the intercellular adhesion of HCC cell lines expressing increasing NeuAcalpha2,3Gal-R. Our model system consisted of the HCC SW48 cell line, which inherently possesses low levels of cell surface alpha2,3 and alpha2,6 sialoglycans. To generate SW48 clonal variants with elevated cell surface NeuAcalpha2,3Gal-R linkages, we transfected the expression vector, pcDNA3, containing either rat liver cDNA encoding Galbeta1,3(4)GlcNAc alpha2,3 sialyltransferase (ST3Gal III) or human placental cDNA encoding Galbeta1,3GalNAc/Galbeta1,4GlcNAc alpha2,3 sialyltransferase (ST3Gal IV) into SW48 cells. Selection of neomycin-resistant clones (600 microgram G418/ml) having a higher percentage of cells expressing NeuAcalpha2,3Gal-R (up to 85% positive Maackia amurenis agglutinin staining compared with 30% for wild type cells) was performed. These ST3Gal III and ST3Gal IV clonal variants demonstrated increased adherence to IL-1beta-activated human umbilical vein endothelial cells (HUVEC) (up to 90% adherent cells compared with 63% for wild type cells). Interestingly, ST3Gal III and ST3Gal IV clonal variants also bound non-activated HUVEC up to 4-fold more effectively than wild type cells. Cell surface NeuAcalpha2,3Gal-R expression within the various SW48 clonal variants correlated directly with increased adhesion to HUVEC (r=0.84). Using HCC HT-29 cells, which express high levels of surface NeuAcalpha2,3Gal-R, addition of synthetic sialyl, sulfo or GalNAc Lewis X structures were found to specifically inhibit intercellular adhesion. At 1.0mM, NeuAcalpha2,3Galbeta1,3(Fucalpha1, 4)GlcNAc-OH and Galbeta1,4(Fucalpha1,3)GlcNAcbeta1,6(SE-6Galbeta1++ +, 3)GalNAcalpha1-O-methyl inhibited HT-29 cell adhesion to IL-1beta-stimulated HUVEC by 100% and 68%, respectively. GalNAcbeta1, 4(Fucalpha1,3)GlcNAcbeta1-O-methyl and GalNAcbeta1,4(Fucalpha1, 3)GlcNAcbeta1,6Manalpha1,6Manbeta1-0-C30H61, however, did not possess inhibitory activity. In conclusion, these studies demonstrated that cell surface NeuAcalpha2,3Gal-R expression is involved in HCC cellular adhesion to HUVEC. These specific carbohydrate-mediated intercellular adhesive events may play an important role in tumor angiogenesis, metastasis and growth control.
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PMID:Cell surface n-acetylneuraminic acid alpha2,3-galactoside-dependent intercellular adhesion of human colon cancer cells. 1008 Sep 50

Decorin is a member of the small leucine-rich proteoglycan (SLRP) gene family that has recently become a focus in various areas of cancer research. The decorin protein consists of a core protein and a covalently linked glycosaminoglycan chain. Decorin binds to collagens type I, II and IV in vivo and promotes the formation of fibers with increased stability and changes in solubility. Further, the decorin core protein binds to growth factors, including transforming growth factor-beta (TGF-beta), to other intercellular matrix molecules such as fibronectin and thrombospondin, and to the decorin endocytosis receptor. Decorin may directly interfere with the cell cycle via the induction of p21WAF1/CIP1 (p21), a potent inhibitor of cyclin-dependent kinases (CDKs). Here, we discuss interactions of decorin with TGF-beta and with p21, both of which are relevant to carcinogenesis and tumor progression. TGF-beta is released by tumors of various histogenetic origins and promotes immunosuppression in the host and tumor immune escape by induction of growth arrest and apoptosis in immune cells, by downregulation of MHC II antigen expression and by changes in the cytokine release profiles of immune and tumor cells. Moreover, TGF-beta may modulate tumor growth in an autocrine and paracrine fashion, may mediate drug resistance, and may facilitate tumor angiogenesis. Decorin binds to TGF-beta, thus inhibiting its bioactivity, and is a direct or indirect negative modulator of TGF-beta synthesis. Ectopic expression of decorin results in the regression of rat C6 gliomas, an antineoplastic effect attributed to the reversal of TGF-beta-induced immunosuppression. On the other hand, de novo expression of decorin in colon cancer cells and some other tumor cells, even though not in glioma cells, results in an upregulation of p21 expression and a cell cycle arrest, presumably in a TGF-beta-independent manner. Decorin expression is downregulated in many tumors but upregulated in the peritumoral stroma. By virtue of its growth regulatory and immunomodulatory properties, decorin promises to become a novel target for the experimental therapy of human cancers.
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PMID:Transforming growth factor-beta and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth. 1038 66

Vascular endothelial growth factor (VEGF) is a most potent angiogenic molecule. In this article, we demonstrated that VEGF is participated in the tumor angiogenesis of hepatocellular carcinoma, esophageal cancer, and pancreatic cancer. Furthermore, we revealed that VEGF is one of the molecules which are responsible for metastasis and prognosis in esophageal cancer and colon cancer. Although the mechanism on the induction of VEGF gene is still unclear in human cancer tissue, we obtained the informative evidence indicating that p53 mutation is involved in VEGF expression of esophageal cancer. Our experimental study with stable transfectant of VEGF gene provided the confirmative results showing that VEGF gene induces neovascularization in and around tumor and that VEGF augment metastastic potential by accelerating proliferative activity after reaching the target organ.
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PMID:Implication of vascular endothelial growth factor in the development and metastasis of human cancers. 1045 2

We demonstrated in this study that inhibition of intra-hepatic growth of colon cancer by TAC-101 is mediated by inhibition of angiogenesis. In vitro experiments showed that TAC-101 inhibited the proliferation of murine hepatic sinusoidal endothelial (HSE) cells induced by coculture with murine colon 26-L5 (L5) cells. HSE cell proliferation was also enhanced by conditioned medium of L5 cells (CM-L5), and this enhancement of proliferation was abrogated by anti-vascular endothelial growth factor antibody. CM-L5 also induced in vitro tube formation of HSE cells on Matri-gel, and this activity of CM-L5 was abrogated by TAC-101 in a concentration-dependent manner. On the other hand, p.o. administration of TAC-101 inhibited tumor-induced angiogenesis in vivo and decreased the weights of L5 tumors in the mouse liver. Reverse transcriptase-PCR analysis using in vivo tumor tissue suggested that repression of vascular endothelial growth factor expression by TAC-101 was associated with the antiangiogenic activity. TAC-101 alone and 5-fluorouracil (5-FU)/D,L-leucovorin (LV) significantly inhibited the intrahepatic growth of L5 tumors (P = 0.002 and 0.001, respectively), whereas 5-FU alone did not (P = 0.088). When TAC-101 was administered with 5-FU/LV, marked enhancement of antitumor activity was observed (95% inhibition; P<0.001). This enhanced antitumor effect was also observed in experiments using Co-3 human colon adenocarcinoma. Concurrent treatment with TAC-101 and 5-FU/LV and sequential treatment with 5-FU/LV followed by TAC-101 resulted in significant augmentation of antitumor activity against Co-3 (overall P = 0.007 and 0.015, respectively). These findings indicate that TAC-101 inhibits tumor angiogenesis and suggest that it may be effective against hepatic metastasis of colon cancer.
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PMID:Inhibition of angiogenesis and intrahepatic growth of colon cancer by TAC-101. 1049 97

The cyclooxygenase (COX) enzymes catalyze a key step in the conversion of arachidonate to PGH2, the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases. Prostaglandins play critical roles in numerous biologic processes, including the regulation of immune function, kidney development, reproductive biology, and gastrointestinal integrity. There are two COX isoforms, which differ mainly in their pattern of expression. COX-1 is expressed in most tissues, whereas COX-2 usually is absent, but is induced by numerous physiologic stimuli. Surprisingly, disruption of Cox1 (Ptgs1) in the mouse did not result in gastrointestinal abnormalities. cox-2 (Ptgs2) null mice show reproductive anomalies and defects in kidney development. Epidemiologic, animal, and human data indicate that NSAIDs, inhibitors of cyclooxygenase, are chemopreventive for colon cancer. COX-2 is overexpressed in 50% of benign polyps and 80-85% of adenocarcinomas. Offspring from cox-2 null by Apcdelta716 matings exhibit an 86% reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth. The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/ or immune function.
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PMID:The role of cyclooxygenases in inflammation, cancer, and development. 1063 Jun 43

Tumor growth and metastasis are dependent on angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in the angiogenesis of numerous solid malignancies including colon cancer. Evidence from preclinical and clinical studies indicates VEGF is the predominant angiogenic factor in human colon cancer and is associated with formation of metastases and poor prognosis. Based on these results, it was hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastasis. To test this hypothesis, the authors evaluated the ability of a small molecule inhibitor specific for the tyrosine kinase VEGF receptor Flk-1/KDR (SU5416) or multiple tyrosine kinase receptors (SU6668) to inhibit tumor angiogenesis and metastasis in a model of colon cancer hepatic metastasis. Both SU5416 and SU6668 inhibited metastases, microvessel formation, and cell proliferation while increasing tumor cell and endothelial cell apoptosis. These results showed that targeting the VEGF receptor/ligand system is a rational approach to inhibiting tumor growth and prolonging survival.
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PMID:Vascular endothelial growth factor in human colon cancer: biology and therapeutic implications. 1080 85

Tumor angiogenesis is essential for tumor growth and tumor metastasis, and it depends on angiogenic factors produced by tumor cells and/or infiltrating cells in tumor tissue. In this study, we evaluated the clinical significance of the expression of angiogenin, which is a potent angiogenic protein, and the relationship between its mRNA expression and focal macrophage infiltration in colorectal cancer. Furthermore, we investigated the induction of angiogenin mRNA expression by proinflammatory cytokines mainly produced by inflammatory cells in tumor tissues. When we examined the relationship between the mRNA expression of angiogenin, by semiquantitative reverse transcription-PCR, and clinicopathological features in 65 patients with colorectal cancer, there was a significant difference in the vascular involvement, lymph node metastasis, liver metastasis, and advanced stage in patients with high-expression of angiogenin compared with low expression (P < 0.05). With regard to prognosis, the survival time for subjects in the high angiogenin mRNA group (tumor:normal ratio >1.9) was significantly worse (P < 0.05). When we examined the localization of angiogenin in colorectal cancer, immunohistochemical analysis in 65 patients with colorectal cancer revealed that angiogenin was predominantly expressed in cancer cells compared with stromal cells or normal tissues. The intensity of staining of angiogenin was significantly correlated with microvessel counts and focal macrophage infiltration counts (P < 0.05). In an in vitro study, interleukin-1beta and tumor necrosis factor-alpha induced angiogenin mRNA expression in colon cancer cells in a dose- and time-dependent manner, and these cytokines significantly upregulated the expression of angiogenin mRNA, especially in colon cancer cells rather than in other cells in the stroma of tumor tissues (fibroblasts, tumor infiltrating lymphocytes, macrophages). These results suggest that tumor angiogenesis in colorectal cancer may be advanced, at least in part, by angiogenin induced by proinflammatory cytokines derived from infiltrating macrophages.
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PMID:Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. 1099 42


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