UMLS:C0001430 - FACTA Search

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

Query: UMLS:C0001430 (adenoma)
21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors. This observation suggests a pathobiological role of tumor-associated NO production. Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression. Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues). Only low levels were found in the surrounding normal tissue. NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung. NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01). Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein bands at Mr 125,000-Mr 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody. However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation. Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ.
...
PMID:Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. 944 14

Circulating vascular endothelial growth factor (VEGF) was measured in gastric and colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA). Firstly, serum and plasma samples were collected from 20 normal controls to compare the values of VEGF and to determine which specimen type was most suitable for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF levels under the limit of detection (15 pg/ml) and the levels of the remaining three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time-course test of two normal controls serum VEGF values increased markedly between 30 and 60 min and remained high, whilst plasma VEGF values were low up to 480 min. Thus, plasma samples are more suitable for the measurement of circulating VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8 advanced without metastasis and 18 metastatic) before treatment. An extremely high plasma concentration of VEGF was seen in some cancer patients with metastasis. To discriminate these patients, a cut-off level was determined, considering both the distribution of the sample concentration and the upper limit of 95% confidence area of VEGF in the cancer patients without metastasis. The cut-off value was 108 pg/ml and most cancer patients without metastases had VEGF levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels were higher than the cut-off value. Survival was also analysed in the patients with metastasis. It was significantly longer in the patients with low VEGF levels (below the cut-off) than in those with high VEGF levels (logrank test, P = 0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer) were treated with systemic chemotherapy, and their pretreatment levels of plasma VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation to response. The response to chemotherapy was significantly higher in patients with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P = 0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma VEGF is a useful marker for tumour metastasis and patient survival, and a possible predictive factor for the response of patients with gastrointestinal cancer to chemotherapy.
...
PMID:Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer. 1007 Mar 8

Activation of hepatocyte growth factor/scatter factor (HGF/SF) in the extracellular milieu is a critical limiting step in the HGF/SF-induced signaling pathway mediated by Met receptor tyrosine kinase, which has potentially important roles in tumor biology and progression. However, little is known concerning the regulation of HGF/SF activation in tumors. Immunoblot analysis revealed that the activation of HGF/SF was enhanced significantly in colorectal carcinoma tissues compared with the corresponding normal mucosa. Serum-free conditioned media of cultured human colorectal carcinoma cell lines contained HGF/SF-activating activity, and the addition of a single-chain precursor form of HGF/SF to the serum-free culture of these cells resulted in HGF/SF-dependent modulation of cellular phenotypes, such as increased scattering and enhanced secretion of vascular endothelial growth factor. This processing activity was enhanced by thrombin treatment but was inhibited significantly by a neutralizing antibody against HGF activator (HGFA), a factor XIIa-like serine proteinase believed to be expressed mainly in the liver. The activity was also inhibited by recombinant HGFA inhibitor type 1 (HAI-1). The presence of HGFA mRNA and secretion of HGFA protein were confirmed in the cell lines. Therefore, extrahepatic expression of HGFA in the colorectal carcinoma cells could be responsible for the single-chain HGF/SF-processing activity of the cells. We examined the expression of HGFA and HAI-1 in human colorectal mucosa and adenoma-carcinoma sequence. Immunohistochemically, HGFA was stained weakly in the normal enterocytes, and immunoreactivity was increased modestly in the neoplastic differentiation. The subcellular localization of HGFA immunoreactivity was altered in carcinoma cells showing basal or cell-stroma interface staining patterns, compared with normal and adenoma cells with a supranuclear or apical staining pattern. In contrast to HGFA, the expression of HAI-1 decreased significantly in carcinoma cells relative to the adjacent normal or adenoma cells, indicating that the net balance between HGFA and HAI-1 shifts in favor of HGFA in carcinomas. In fact, pro-HGFA and the active form of HGFA proteins increased in carcinoma tissue compared with the corresponding normal mucosa. It was concluded that HGFA is expressed in colorectal mucosa and tumors and could be involved in the activation of HGF/SF in colorectal carcinomas. Therefore, the balance between HGFA and HAI-1 could play an important role in the regulation of HGF/SF activity in colorectal carcinomas.
...
PMID:Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma. 1108 39

The aim of this study was to investigate the effect of short-term treatment with losartan, a selective and competitive angiotensin II (AngII) receptor blocker, on vascular endothelial growth factor (VEGF), active renin and kallikrein activity (KA) in patients with essential hypertension and primary aldosteronism. Nine patients with primary aldosteronism (5 with Conn adenoma and 4 with idiopathic hyperaldosteronism) and 9 patients with essential hypertension were included in the study. Systolic and diastolic blood pressure decreased significantly after losartan treatment in both patient groups. Plasma and urinary Kallikrein activity were significantly higher in primary aldosteronism in comparison with essential hypertension. There were no significant changes in the active renin and aldosterone in patients with primary aldosteronism after treatment. Plasma and urinary KA decreased significantly after losartan administration in both groups. Serum VEGF levels in primary aldosteronism were not significantly different from those in essential hypertension and did not change significantly after treatment in either group. In conclusion, losartan, in usual therapeutic doses, lowers blood pressure in patients with primary aldosteronism and essential hypertension. This marked antihypertensive effect in primary aldosteronism could be explained predominantly by blockade of tissue renin-angiotensin system (RAS). The variations in KA could be due to hemodynamic changes. VEGF is not likely to be involved in the action of losartan.
...
PMID:Effect of short-term losartan treatment in patients with primary aldosteronism and essential hypertension. 1152 16

Arachidonic acid is metabolized to prostaglandin H(2) (PGH(2)) by cyclooxygenase (COX). COX-2, the inducible COX isozyme, has a key role in intestinal polyposis. Among the metabolites of PGH(2), PGE(2) is implicated in tumorigenesis because its level is markedly elevated in tissues of intestinal adenoma and colon cancer. Here we show that homozygous deletion of the gene encoding a cell-surface receptor of PGE(2), EP2, causes decreases in number and size of intestinal polyps in Apc(Delta 716) mice (a mouse model for human familial adenomatous polyposis). This effect is similar to that of COX-2 gene disruption. We also show that COX-2 expression is boosted by PGE(2) through the EP2 receptor via a positive feedback loop. Homozygous gene knockout for other PGE(2) receptors, EP1 or EP3, did not affect intestinal polyp formation in Apc(Delta 716) mice. We conclude that EP2 is the major receptor mediating the PGE2 signal generated by COX-2 upregulation in intestinal polyposis, and that increased cellular cAMP stimulates expression of more COX-2 and vascular endothelial growth factor in the polyp stroma.
...
PMID:Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. 1153 9

Details of concurrent expression of angiogenic growth factors (AGFs) and microvessel density (MVD) in human colorectal adenomas and carcinomas remain obscure. Eighty lesions, 20 each from colorectal adenoma, Tis, T1 and T2 cancers were evaluated immunohistochemically for basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (dThdPase) and MVD. MVD (p = 0.0001) and bFGF expression (p = 0.0001) increased in the order of adenoma, Tis, T1 and T2 cancers. VEGF expression was same in adenomas and cancers while dThdPase was weak in adenomas but strongly expressed in invasive carcinomas ( > T1). MVD had positive correlation with tumour size in small (< or = 4 cm) colorectal cancers. Concurrent expression of AGFs was noticed in invasive carcinomas. bFGF seems to be the strongest among the three AGFs expressed during colorectal carcinogenesis and had a significant correlation with tumour MVD. Concurrent expression of multiple AGFs is a crucial step in the transition from non-invasive to invasive carcinoma.
...
PMID:Concurrent expression of angiogenic growth factors and neovascularization during tumourigenesis in colorectal carcinoma patients. 1166 35

We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carcinoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA expression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenomatous polyps. Immunohistochemistry and ELISA assessed protein expression. VEGF-D mRNA expression was significantly lower in both polyps and CRCs compared with normal mucosa (P=.0002 and.002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and.004, respectively), but not polyps (P=.22 and P=.5, respectively). Receptor expression was similar in tumor tissue and normal mucosae. Tumors with lymph node metastases had significantly higher levels of VEGF-A compared with non-metastatic tumors (P=.043). There was no association between VEGF-C or VEGF-D and lymphatic spread. The decrease in VEGF-D occurring in polyps and carcinomas may allow the higher levels of VEGF-A and VEGF-C to bind more readily to the VEGF receptors, and produce the angiogenic switch required for tumor growth. Increased expression of VEGF-A within CRCs was associated with lymphatic metastases, and therefore, this member of the VEGF family may be the most important in determining metastatic spread.
...
PMID:VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. 1168 53

To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout (Apc(Delta716)) mice, a model for human familial adenomatous polyposis. We scored MVD also in several compound mutants carrying Apc(Delta716), namely, mice with an additional mutation in Smad4, in which the polyps progress into invasive adenocarcinomas; mice with a cyclooxygenase (COX)-2 gene (Ptgs2) mutation, in which adenoma growth is suppressed; and mice with prostaglandin E(2) EP receptor gene mutations. In both simple Apc(Delta716) and compound Apc(Delta716) Smad4 mutants, MVD increased in a polyp size-dependent manner only in the polyps expanded beyond a threshold of about 1 mm in diameter. These results indicate that tumor angiogenesis is stimulated only after tumors grow to a certain size, and this angiogenic switch is common to both benign adenomas and malignant adenocarcinomas. In Apc(Delta716) polyposis attenuated by the COX-2 gene mutation, in contrast, MVD did not increase even in polyps larger than 1 mm. The same phenomenon was observed in the compound mutant mice with Apc(Delta716) and the EP(2) receptor gene mutations, but not in other EP compound mutants. We also immunohistochemically studied COX-2 and angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor. Interestingly, expression of these proteins was also increased in polyps larger than 1 mm. These results suggest that, in both benign and malignant mouse intestinal tumors, stromal expression of COX-2 results in elevated prostaglandin E(2) levels that stimulate cell surface receptor EP(2), followed by induction of vascular endothelial growth factor that causes tumor angiogenesis.
...
PMID:Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps. 1180 2

The pivotal role of vascular endothelial growth factor (VEGF-A) in the regulation of angiogenesis, in particular in the onset and maintenance of tumor angiogenesis, has been demonstrated repeatedly in experimental model systems and, more recently, in clinical trials. Experimental evidence has also suggested that up-regulated expression of VEGF-A may cooperate with other genetic or epigenetic changes to induce or accelerate tumor progression to invasive and metastatic cancers. Here we report the generation of transgenic mouse lines that express human VEGF-A165 under the control of the rat insulin promoter in the beta cells of pancreatic islets of Langerhans (Rip1VEGF-A). These mice do not exhibit detectable changes in islet development, vascularization, or physiology. Intercrosses of these mice with a transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2) result in an earlier onset of tumor angiogenesis and with it accelerated tumor growth and mortality. The transition from benign tumors (adenoma) to malignant tumors (carcinoma) is modestly accelerated; however, tumor metastases are not observed. Our findings indicate that in beta-cell tumorigenesis, overexpression of VEGF-A165 accelerates the onset of tumor angiogenesis and with it tumor progression but is not sufficient to induce tumor metastasis.
...
PMID:Overexpression of vascular endothelial growth factor-A165 enhances tumor angiogenesis but not metastasis during beta-cell carcinogenesis. 1180 16

Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been reported to be significantly related to carcinogenesis or progression of various cancers. However, there has been no report on the relation between COX-2 and VEGF overexpression in pancreatic tumors. We investigated the overexpression of COX-2 and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT) and invasive ductal carcinoma (IDC) and examined the relationship with clinicopathological factors and the correlation between these immunoactivities in IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10 areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary, 47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However, in IDC it was 47.8%. Only lymph node metastasis correlated significantly with VEGF overexpression (p=0.04), while the other factors had no significant relationships with either COX-2 or VEGF overexpression. There was a statistically significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001), in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no statistically significant relationship in IDC. In conclusion, we demonstrate evidence of COX-2 and VEGF overexpression in human pancreatic tumors. Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be more effective in IPMT than in IDC, because of the strong correlation of both factors especially in IPMT.
...
PMID:Expression of cyclooxygenase-2 and vascular endothelial growth factor in pancreatic tumors. 1206 5

1 2 3 4 5 6 7 Next >>