Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteoglycans are macromolecules containing a core protein to which glycosaminoglycan chains are covalently attached. The family contains several members with different structures and various functions. Some of them are elements of the extracellular matrix, while others are located to the cell surface playing important role in cell-cell and cell-extracellular matrix interactions. Present paper discusses the possible consequences of the alterations of proteoglycans observed in liver cirrhosis and liver tumors. It has to be emphasized however, that they are also involved in the pathomechanism of arteriosclerosis, Alzheimer-disease, immune diseases, arthritis, tumor progression and metastasis formation.
 ...
PMID:[Proteoglycans (their structure, function and role in liver diseases)]. 841 46

Angiogenesis plays a pivotal role not only in wound healing and tumor progression but also in diabetic angiopathy, arteriosclerosis, and collateral formation of obstructive vascular diseases. Vascular endothelial growth factor (VEGF) is now thought to be an endothelium-specific and potent angiogenic factor. We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from porcine brain, is produced by endothelial cells and proposed that CNP can exert control over vascular tone and growth as a local vascular regulator. In the present study, we examined the effect of VEGF on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP we developed. VEGF (1 to 100 ng/mL) dose-dependently suppressed CNP secretion from cultured bovine endothelial cells, and 100 ng/mL VEGF suppressed endothelial CNP secretion to 28% of control levels (31.7 +/- 5.5 versus 8.9 +/- 0.8 fmol/mL, vehicle versus VEGF). VEGF also suppressed CNP mRNA expression in endothelial cells 9 hours after administration. In contrast, basic fibroblast growth factor (20 ng/mL), an endothelium-nonspecific angiogenic factor, significantly stimulated CNP secretion by 290%. These results indicate that VEGF can regulate vascular tone and growth in the process of angiogenesis through suppression of endothelial secretion of CNP, which is an endothelium-derived vasorelaxing and growth-inhibitory peptide.
 ...
PMID:Vascular endothelial growth factor suppresses C-type natriuretic peptide secretion. 861 45

Contradictary results have been reported indicating both increased and reduced risks for malignancies in diabetic patients. This may possibly be due to difficulties in the clinical diagnosis of carcinomas and inaccuracies in the determination of diabetic conditions in the autopsy studies. Since glomerular microangiopathy is a typical feature of long-term diabetes, we performed a retrospective statistical analysis on 5000 consecutive, non-selected autopsy cases with particular reference to the presence/absence of microangiopathy in diabetic individuals. In our study group, we found a total incidence of 9.8% (n = 488) diabetic patients of which 213 (4.3%) had a histologically confirmed significant glomerulosclerosis and a total of 34% patients with verified carcinoma (n = 1699). The age- and sex ratios were matched between diabetic, non-diabetic and carcinoma patients. Systemic and coronary arteriosclerosis were significantly higher in diabetics than non-diabetics (p < 0.0001). Most interestingly, the rate of carcinomas in the diabetic group with nodular and diffuse glomerulosclerosis was 2.5- (p < 0.0001) and 1.9-fold (p < 0.0027), respectively, lower than in the non-diabetic group. In addition, the statistical evaluation showed in the glomerulosclerotic diabetic group significantly lower rates of metastasis. Our retrospective statistical analysis on an unselected series of autopsy cases thus provides evidence that diabetes mellitus with glomerulosclerosis is associated with a significantly lower frequency of carcinomas when compared to individuals without renal microangiopathy. Since TGF-beta is assumed to play a crucial role both in diabetes and carcinogenesis/tumor progression, our findings suggest an altered cell-matrix interaction in diabetes, possibly exerted by chronic TGF-beta overexpression.
 ...
PMID:Patients with diabetes-induced microangiopathy show a reduced frequency of carcinomas. 989 Dec 30

Mammalian sialidases (NEU1, NEU2, NEU3 and NEU4) that remove sialic acids from glycoconjugates have been implicated in diverse cellular functions. Human sialidases are involved in the development of various disease states such as cancer, diabetes and arteriosclerosis. Unregulated acidic sialidase NEU1 activity is associated with the pathogenesis of lysosomal storage disorder (LSD) sialidosis, abnormal immune responses and cancer progression. Obesity is closely related to several chronic diseases such as diabetes, cardiovascular diseases, hyperlipidemia or hypertension that are associated with metabolic syndrome. We examined fluctuations in mRNA levels and sialidase activities of NEU1 in two strains of obese and diabetic mice to assess the involvement of NEU1 in obesity. The activity of NEU1 was preferentially higher in epididymal fat and lower in the livers of two strains of obese and diabetic mice. Fluctuations in NEU1 activity might be associated with the pathological status of these tissues in obesity.
 ...
PMID:Acidic sialidase activity is aberrant in obese and diabetic mice. 2372 24

The tetraspanin Tspan8 supports via associated integrins and proteases tumor progression and angiogenesis. To shed light on its activities in non-transformed cells, we generated a Tspan8 knockout (ko) mouse, comparing leukocyte migration, angiogenesis, wound healing and tumor growth with wild type, CD151ko and Tspan8/CD151ko (dbko) mice. CD151ko mice were included as CD151 activities resemble that of Tspan8, and dbko mice to exclude mutual substitution. Tspan8ko and dbko mice show no pathological phenotype. However, delayed type hypersensitivity reactions are mitigated in Tspan8ko mice, angiogenesis is severely impaired in Tspan8ko, CD151ko and dbko mice, with Tspan8 mostly affecting lymphangiogenesis. Distinct contributions of CD151 and Tspan8 to skin wound healing rely on preferentially CD151 anchoring basal keratinocytes and Tspan8 promoting motility. Proliferation of wounded skin keratinocytes is not affected. Metastasis formation of a melanoma and a Tspan8-expressing pancreatic cancer line was impaired in Tspan8ko and dbko mice, pointing towards a contribution of host Tspan8 to tumor progression. In line with the importance of tetraspanins in exosome-mediated intercellular communication, defects became mitigated by Tspan8/CD151-competent serum exosomes, which offers a most promising therapeutic option for chronic wounds and arteriosclerosis.
 ...
PMID:Distorted leukocyte migration, angiogenesis, wound repair and metastasis in Tspan8 and Tspan8/CD151 double knockout mice indicate complementary activities of Tspan8 and CD51. 2936 56