Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
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PMID:The prognostic molecular markers in hepatocellular carcinoma. 1204 56

We have previously reported that combretastatin-A4 prodrug (CA4P), anantitubulin/antiangiogenic agent isolated from the South African willow tree Combretum caffrum, induced cell death primarily through mitotic catastrophe in a panel of human B-lymphoid tumors. In this study, we investigated the molecular aspects of the mitotic catastrophe and whether or not it shares the same pathways of apoptosis. For this we studied the effect of CA4P on selected markers of apoptosis [caspases 9 and 3, poly(ADP-ribose) polymerase (PARP), bcl-2, and bax] and G2-M protein regulators (p53, MDM2, 14-3-3sigma, GADD45, cdc2, cdc25, chk1, wee1, p21, and cyclin B1). The chronic lymphocytic leukemia cell line WSU-CLL was used for this purpose. Western blot analysis showed that 24 h of CA4P (5 nM) exposure induces caspase 9 activation and PARP cleavage. However, the addition of Z-Val-Ala-Asp-fluoromethylketone (a general caspase inhibitor) or Z-Leu-Glu(OMe)-His-Asp(OMe)-CH2F (a caspase 9 inhibitor) before CA4P treatment did not block cell death. No change in bcl-2 or bax protein expression was observed. Exposure of WSU-CLL cells to 4 and 5 nM CA4P was associated with overproduction of total p53 and no dramatic change in MDM2, 14-3-3sigma, GADD45, the cyclin-dependent kinase cdc2, its inhibitory phosphorylation, the cdc2-inhibitory kinase (wee1), chk1, or cdc25 hyperphosphorylation. The overaccumulation of p21 and cyclin B1 protein was obvious at 24 h. Furthermore, CA4P treatment showed an increase in the expression of a marker of mitosis (mitotic protein monoclonal-2 antibody) and an overaccumulation of the cyclin B in the nucleus. Our findings suggest that CA4P induces mitotic catastrophe and arrest of WSU-CLL cells mostly in the M phase independent of p53 and independent of chk1 and cdc2 phosphorylation pathways. Apoptosis is a secondary mechanism of death in a small proportion of cells through activation of caspase 9 and PARP cleavage. The two mechanisms of cell death, i.e., mitotic catastrophe and apoptosis, are independent of each other in our model.
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PMID:Combretastatin-A4 prodrug induces mitotic catastrophe in chronic lymphocytic leukemia cell line independent of caspase activation and poly(ADP-ribose) polymerase cleavage. 1217 7

Tetrahydrobiopterin (BH(4)) has been known to be an essential cofactor for the activities of nitric oxide (NO) synthase and aromatic amino acid hydroxylases, which are involved in physiological and pathological processes. In the present study, we report that sepiapterin, the more stable form of BH4 precursor, modulates vascular endothelial growth factor-A (VEGF-A)-induced cell proliferation and adhesion in human umbilical vein endothelial cells (HUVECs). The antiproliferative activity of sepiapterin in VEGF-A-treated HUVECs is associated with inhibition of the expression of cyclin-dependent kinases (Cdks) such as Cdk4 and Cdk2. Pretreatment with NO synthase inhibitor does not abrogate the ability of sepiapterin to inhibit VEGF-A-induced cell proliferation and adhesion, indicating that the suppressive effects of sepiapterin on VEGF-Ainduced responses are mediated by NO-independent mechanism. Finally, we show that sepiapterin modulates VEGF-A-induced cell proliferation and adhesion through down-regulation of VEGF receptor-2 downstream signaling pathways. Taken together, these findings represent a novel function of sepiapterin in the regulation of angiogenesis, supporting further development and evaluation of sepiapterin as an antiangiogenic agent.
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PMID:Inhibitory effects of sepiapterin on vascular endothelial growth factor-A-induced proliferation and adhesion in human umbilical vein endothelial cells. 2197 20

Hypertrophic scar (HS) is a pathological scar that particularly occurs after traumatic injuries, surgical procedures and burning. Abnormal activation of hypertrophic scar fibroblasts (HSFs) intensifies fibrosis during wound healing. Our previous studies demonstrated that recombinant human endostatin (rhEndostatin) prevented synovial thickening in adjuvant arthritis (AA) rats via inhibition of proliferation and enhancement of apoptosis in synovial fibroblasts. However, the effect of this protein on HSF proliferation is not known. This study investigated the inhibitory effect of rhEndostatin on the proliferation of cultured HSFs in a rabbit ear model. MTT assay and flow cytometric detection were performed to investigate HSF proliferation and cell cycle progression, respectively. The expression levels of p53, p21, cyclinD1, cyclin-dependent kinase 4 (CDK4) and proliferating cell nuclear antigen (PCNA) in HSFs were detected using real-time PCR and Western blotting. Our data revealed that HSFs treated with rhEndostatin were significantly inhibited in a concentration-dependent manner with an IC50 value of 100mg/L. Also, rhEndostatin (100mg/L) primarily induced G0/G1 and partially G2/M cell cycle arrest of HSFs. There were significant decreases in the expression levels of p53, p27, CDK4, cyclinD1 and PCNA in HSFs treated with rhEndostatin. In conclusion, rhEndostatin inhibited HSF proliferation via G0/G1 and/or G2/M phase arrest of the cell cycle, which was partially due to the down-regulation of cyclinD1, CDK4 and PCNA. These findings suggest that rhEndostatin may reduce scar hypertrophy in vivo via inhibition of HSF proliferation and may be a novel agent for HS treatment.
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PMID:Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model. 2769 24