UMLS:C0009402 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0009402 (colorectal cancer)
53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plant sterol guggulsterone has been shown to exert anti-tumor effects, making it a candidate chemotherapeutic agent. We investigated the anti-tumor effects of guggulsterone on colon cancer cells and elucidated the underlying molecular mechanisms related to angiogenesis. The apoptotic effects of guggulsterone were examined by cell survival assay. Western blot analysis was used to determine the levels of various down-stream intracellular proteins involved in angiogenesis, including signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1alpha (HIF-1alpha) and aryl hydrocarbon receptor nuclear translocator (ARNT). Using chromatin immunoprecipitation assay, we tested whether guggulsterone affects the recruitment of STAT3, ARNT and HIF-1alpha to the human VEGF promoter. To investigate the effect of guggulsterone on vascular endothelial cell migration and invasion, tube formation and migration assays were conducted using human umbilical vein endothelial cells (HUVECs). Matrix metalloproteinase (MMP)-2 and -9 activities were measured by gelatin zymography. Guggulsterone significantly reduced cell viability in colon cancer cells in a dose-dependent manner and blocked VEGF, ARNT and STAT3 expression prominently in hypoxic conditions. The recruitment of STAT3 and ARNT, but not HIF-1alpha, to the VEGF promoter was inhibited by guggulsterone treatment. HUVECs produced much foreshortened and severely broken tubes and showed decreased migration activity under guggulsterone effects. In addition, zymography revealed that MMP-2 and -9 enzyme activities were markedly lower in the presence of guggulsterone. The results of this study suggest that guggulsterone not only induces apoptosis, but also inhibits angiogenesis and metastasis in colon cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of colorectal cancer.
...
PMID:Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells. 1902 Jul 9

We present a case of multiple colorectal liver metastases with macroscopic portal vein thrombi. A 55-year-old woman presented to us with rectosigmoid cancer and presented with two liver metastases. The tumor in the posterior sector was associated with invasion of first order branches of the portal vein. We performed low anterior resection, hepatic posterior sectorectomy and partial left anterior sectorectomy. Both the colorectal cancer and liver tumors exhibited histological characteristics of moderately differentiated adenocarcinoma with a substantial amount of mucin production. The liver metastases were associated with prominent tumor thrombi in many branches of the portal vein. Stronger staining for endoglin (CD 105) than for Fas ligand (Fas L) and matrix metalloproteinase (MMP-2) was observed in both the colorectal cancer and metastatic liver tumor cells. Expression of the vascular endothelial growth factor within the tumor cells was seen in both the colorectal cancer as well as the metastatic liver tumor cells. Six months after the operation, she was diagnosed to have multiple, more than about 20 liver metastases, and in 9 months after the operation, the patient died. The colorectal cancer with liver metastases associated with portal vein tumor thrombosis was poor prognosis, found neoplastic microvessel formation.
...
PMID:Macroscopic portal vein tumor thrombi of liver metastasis from colorectal cancer. 1908 48

A variety of susceptibility genes have been associated with cancer but definitive conclusions have been difficult to draw partly hampered by the small number of subjects in each study. We undertook a comprehensive genetic meta-analysis of all matrix metalloproteinase (MMP) genes investigated using an allelic-association case-control model in the 3 major cancers of lung, breast and colorectal cancer. Electronic databases were searched until and including July 2008 for any MMP genetic association study in lung, breast and colorectal cancer. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models. Twenty-five studies addressing 5 polymorphisms in 4 genes were analyzed among 30,651 individuals (15,328 cases and 15,253 controls). The MMP-1 nt-1607 polymorphism was significantly associated with colorectal cancer in both the dominant (OR, 1.66; 95% CI, 1.14-2.42; p = 0.008) and recessive (OR, 1.59; 95% CI, 1.15-2.20; p = 0.005) models. MMP-2(1306C-->T) (OR, 0.53; 95% CI, 0.40-0.72; p < 0.0001) and 735(C-->T) (OR, 0.65; 95% CI, 0.53-0.79; p < 0.0001) were significantly associated with protection against lung cancer. No association was found with the MMP 1, 2, 3 or 9 polymorphisms with breast cancer, MMP-1, 3 or 9 with lung cancer or MMP-2, 3 or 9 with colorectal cancer. There may be a genetic influence in the development of colorectal and lung cancer. Subjects with the MMP-1 nt-1607 polymorphism have an increased association with colorectal cancer. Those homozygous for either the MMP-2/1306T or 735T allele may be at reduced risk of lung cancer, although the evidence base is small.
...
PMID:Polymorphisms of matrix metalloproteinases 1, 2, 3 and 9 and susceptibility to lung, breast and colorectal cancer in over 30,000 subjects. 1950 56

Fully active MMP-2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. Our study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP-2 is an effective indicator of colorectal cancer compared to pro-MMP-2 or pro-MMP-9. MMP-2 and MMP-9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer-assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP-2, pro-MMP-2 and pro-MMP-9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP-2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10-fold) than in normal mucosa. Levels of pro-MMP-2 and pro-MMP-9, but not active MMP-9, activities were also significantly higher in cancers versus normal. However, active MMP-2 activity provided the most effective test for the presence of cancer (p<0.0.0001) with an effect size statistically significantly larger than for either pro-MMP-2 or pro-MMP-9. Receiver operating characteristic (ROC) curves demonstrated that a cut-off for active MMP-2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%.
...
PMID:Active MMP-2 effectively identifies the presence of colorectal cancer. 1955 56

Common prognostic factors do not fully predict clinical outcomes in colorectal cancer, one of the most common malignancies in developed countries. Therefore, biological prognostic markers are under investigation. We investigated the prognostic value of expression of matrix metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-2 and TIMP-3) in rectal carcinoma to predict survival of the patients. Retrospective analysis of clinicopathological findings of 64 patients who underwent rectal resection due to carcinoma and were followed-up from 2 to 96 months (median 48) was performed. Semi-quantitative scoring was used to assess the expression levels of MMP-2, MMP-9, TIMP-2 and TIMP-3 in rectal carcinoma. During the follow-up, 28 patients died. The deceased patients demonstrated significantly higher expression of MMP-9 and lower expression of TIMP-3 in parenchyma of carcinoma and lower expression of TIMP-2 in stroma of carcinoma, compared to survivors. Moreover, the deceased patients were associated with advanced tumor, metastases in lymph nodes and distant metastases. According to univariate analysis longer survival was predicted by lower expression of MMP-9 in parenchymal cells (p = 0.03), tumor size (early tumor) (p = 0.026), absence of metastases in lymph nodes (p = 0.02) or distant metastases (p = 0.04). Multivariate analysis revealed that metastases in lymph nodes, higher expression of MMP-9 in parenchyma, and lower expression of MMP-9 in stromal cells significantly increased mortality. Expression of MMP-9 in rectal carcinoma is a prognostic marker for overall survival. It is important to identify the origin of MMP-9 to predict better overall survival of the patients.
...
PMID:Matrix metalloproteinase-9 is a prognostic marker to predict survival of patients who underwent surgery due to rectal carcinoma. 2121 4

Metastasis is the final step in tumor progression from a benign cell to a fully malignant cell. The metastatic phenotype results from a wide range of phenotypic changes in the cell from the expression of proteinases, to adhesion molecules, the loss of proteinase inhibitors and tumor suppressor gene function, to name a few. However, the molecular basis for this progression has long been investigated and there does not appear to be a specific genetic alteration responsible for influencing all the changes which occur in a metastatic cell. As mentioned, the proteolytic ability of the cell is a key factor in the malignant phenotype and the expression of matrix metalloproteinases (MMPs) is known to contribute to metastases (1). The gelatinase group (MMP-2 and MMP-9) within this enzyme family has been associated with tumor progression and the active form of MMP-2 has the strongest correlation with the metastatic phenotype in colorectal cancer (2).
...
PMID:Genetic modification of cell lines to enhance their metastatic capability. 2134 Aug 44

Endothelin-1 (ET-1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET-1 stimulated processes involved in tumour stroma production by colonic fibroblasts. Primary human fibroblasts, isolated from normal tissues adjacent to colon cancers, were cultured with or without ET-1 and its antagonists. Cellular proliferation, migration and contraction were measured. Expression of enzymes involved in tumour stroma development and alterations in gene transcription were determined by Western blotting and genome microarrays. ET-1 stimulated proliferation, contraction and migration (p < 0.01 v control) and the expression of matrix degrading enzymes TIMP-1 and MMP-2, but not MMP-3. ET-1 upregulated genes for profibrotic growth factors and receptors, signalling molecules, actin modulators and extracellular matrix components. ET-1 stimulated colonic fibroblast cellular processes in vitro that are involved in developing tumour stroma. Upregulated genes were consistent with these processes. By acting as a strong stimulus for tumour stroma creation, ET-1 is proposed as a target for adjuvant cancer therapy.
...
PMID:Endothelin-1 stimulates colon cancer adjacent fibroblasts. 2144 67

High molecular (above 10 kDa) melanoidins isolated from coffee beans of varying roasting degree were found to be efficient inhibitors for the zinc-containing matrix metalloproteases MMP-1, MMP-2, and MMP-9 with IC(50) values ranging between 0.2 and 1.1 mg/mL in vitro. The inhibitory potential increased with roasting degree. No or only slight inhibition of other zinc-containing peptidases closely related to MMPs, namely, Clostridium histolyticum collagenase and angiotensin converting enzyme, was found, indicating specific structural features of melanoidins to be responsible for the interaction with MMPs. A continuous increase on the apparent molecular weight of melanoidins as well as incorporation of phenolic substances into the melanoidin structure with progress of roasting was observed, concomitant with a significant increase in the carbon/nitrogen of the melanoidins. This suggests that the melanoidins are mainly formed by incorporation of carbohydrates and phenolic compounds onto a proteinaceous backbone. As MMP-1, MMP-2, and MMP-9 play a pivotal role in pathogenesis of colorectal cancer, studies on possible physiological effects of melanoidins are mandatory.
...
PMID:High molecular weight coffee melanoidins are inhibitors for matrix metalloproteases. 2196 1

Phosphatase of regenerating liver (PRL)-3, a member of a subgroup of protein tyrosine phosphatases that can stimulate the degradation of the extracellular matrix, is over-expressed in metastatic colorectal cancer (CRC) relative to primary tumors. To determine whether PRL-3-induced enhancement of migration and invasion is dependent on the expression of matrix metalloproteinases (MMPs), PRL-3 was expressed in DLD-1 human CRC cells. The motility, migration and invasion characteristics of the cells were examined, and metastasis to the lung was confirmed in a nude mouse using PRL-3-overexpressing DLD-1 cells [DLD-1 (PRL-3)]. Migration and invasion of the cells were inhibited by phosphatase and farnesyltransferase inhibitors. Expression of MMPs was enhanced 3- to 10-fold in comparison to control cells, and migration and invasion were partially inhibited by small interfering RNA (siRNA) knockdown of MMP-2, -13 or -14. Importantly, siRNA knockdown of MMP-7 completely inhibited the migration and invasion of DLD-1 (PRL-3) cells, whereas overexpression of MMP-7 increased migration. The expression of MMP-7 was also downregulated by phosphatase and farnesyltransferase inhibitors. It was found that PRL-3 induced MMP-7 through oncogenic pathways including PI3K/AKT and ERK and that there is a relationship between the expression of PRL-3 and MMP-7 in human tumor cell lines. The expression of MMP-13 and -14 was very sensitive to the inhibition of farnesyltransferase; however, the migration and invasion of DLD-1 (PRL-3) cells did not strongly depend on the expression of MMP-13 or -14. These results suggest that the migration and invasion of PRL-3-expressing CRC cells depends primarily on the expression of MMP-7.
...
PMID:Phosphatase of regenerating liver-3 promotes migration and invasion by upregulating matrix metalloproteinases-7 in human colorectal cancer cells. 2213 Oct 18

A proliferation-inducing ligand (APRIL) is overexpressed in most tumor cells and tissues, especially in tumors of the alimentary system, such as colorectal cancer (CRC), gastric cancer, and liver cancer. RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown and holds great promise for the treatment of cancer. In this study, the efficacy of RNAi targeting APRIL was analyzed via relevant experiments on human CRC xenografted in BALB/c nude mice. Both the mRNA and protein levels of APRIL were examined after intratumoral injection of APRIL small interfering RNA (siRNA). Meanwhile, pathological tools were utilized to observe the alterations on the aspects of proliferation, metastasis, apoptosis and cellular necrosis by means of detecting proliferating cell nuclear antigen, Ki-67, MMP-2, MMP-9, TIMP-3, TIMP-4, Bcl-2, Bax and Bcl-xL of CRC. In addition, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and hematoxylin and eosin staining were also conducted to examine cell apoptosis and necrosis. It was found that grafted human colorectal tumor growth and metastasis were obviously inhibited while tumor cell apoptosis and necrosis were induced after in vivo APRIL siRNA injection into nude mice. The data indicated that silencing of the APRIL gene using RNAi may serve as a novel therapeutic strategy for treatment of CRC.
...
PMID:Targeting of colorectal cancer growth, metastasis, and anti-apoptosis in BALB/c nude mice via APRIL siRNA. 2217 May 70

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>