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)

Membrane vesicles of Veillonella alcalescens, grown in the presence of L-lactate and KNO-3, actively transport amino acids under anaerobic conditions in the presence of several electron donors and the electron acceptor nitrate. The highest initial rates of uptake are obtained with L-lactate, followed by reduced nicotinamide adenine dinucleotide, glycerol-1-phosphate, formate, and L-malate.. The membrane vesicles contain the dehydrogenases for these electron donors, and these enzymes are coupled with nitrate reductase. In membrane vesicles from cells, grown in the presence of nitrate, the dehydrogenases are not coupled with fumarate reducatase, and anaerobic transport of amino acids does not occur with fumarate as electron acceptor. Under aerobic conditions none of the physiological electron donors can energize transport. However, a high rate of uptake is observed with the electron donor system ascorbate-phenazine metho-sulfate. This electron donor system also effectively energizes transport under anaerobicconditions in the presence of the electron acceptor nitrate.
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PMID:Amino acid transport in membrane vesicles of obligately anaerobic Veillonella alcalescens. 16 33

Both chemotherapy and chimeric anti-CD20 monoclonal antibodies are effective agents against B-cell non-Hodgkin lymphoma (NHL). However, patients achieving remission are at risk of relapse. To evaluate the effect of the antiangiogenic drug endostatin used alone and after the administration of cyclophosphamide (CTX) or the anti-CD20 antibody rituximab, we generated a new model of human NHL by transplanting Namalwa cells intraperitoneally into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. First, we determined the most effective treatment schedule for the drugs assessed. When administered alone, CTX (3 courses of 75 mg/kg of body weight given intraperitoneally), rituximab (3 courses of 25 mg/kg given intraperitoneally), and endostatin (5 courses of 50 microg given subcutaneously) delayed tumor growth, and CTX was the most effective in controlling bulky disease. When given after chemotherapy or immunotherapy, endostatin effectively induced tumor stabilization. When mice given CTX or rituximab on days 3, 5, and 7 after transplantation were randomly assigned to receive endostatin or phosphate-buffered saline on days 15 to 19, tumor growth was prevented in endostatin-treated mice as long as the drug was administered. Furthermore, administration of endostatin on days 25 to 29 after tumor regrowth still induced significant tumor regression, whereas CTX and rituximab were not effective. The specific antiangiogenic action of endostatin was confirmed by in vitro and in vivo studies indicating that the drug inhibited proliferation and induced apoptosis of endothelial (but not of NHL) cells. In conclusion, sequential administration of chemotherapy and endostatin seems promising for treating bulky NHL, and the less toxic sequential administration of rituximab and endostatin is promising for treating limited disease. (
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PMID:Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma. 1089 63

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.
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PMID:Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus. 1168 3

Tumor growth and metastasis are dependent on the development of new blood vessels. Inhibitors of new vessel growth have been widely investigated as anti-tumor agents. Endostatin, a 20 kDa C-terminal fragment of collagen XVIII inhibits endothelial cell proliferation, induces endothelial cell apoptosis, and can both inhibit and reverse tumor growth in mice. However, human recombinant endostatin has had limited testing against human tissue targets. To investigate the effect of human endostatin on a human vessel target over a broad range of concentrations (10(-l2)-10(-4) M), human placental vein disks were grown for a period of 2 weeks in a 0.3% fibrin clot overlayed with growth medium. Disks from five individual placentas were tested. For each placenta utilized, a control (medium and 20% fetal bovine serum [FBS]) group and a group treated with heparin (300 microg/ml) and hydrocortisone 21-phosphate (350 microg/ml) (heparin-steroid) at a dose known to inhibit angiogenesis were included. Endostatin was tested at concentrations of 10(-12)-10(-4) M in medium containing 20% FBS. The rate of initiation and the angiogenic growth index (on a visually graded semi-quantitative scale of 0-16) were determined for all experimental conditions. Endostatin inhibited angiogenesis in our model only in high concentrations. At 10(-5) M, endostatin did not alter the percent of wells that initiated an angiogenic response, but significantly inhibited subsequent vessel growth. At 10(-4) M, endostatin was able to inhibit both initiation and subsequent new vessel growth. Human endostatin can inhibit the initiation of a human angiogenic response and inhibit the subsequent proliferation of human neovessels when used at high doses in a continuous exposure model.
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PMID:Effect of human recombinant Endostatin protein on human angiogenesis. 1254 68

The stability constants of the supramolecular complexes formed between L ((a,b,c,d)) or their Zn(2+) complexes, and adenosine 5'-triphosphate (ATP) in aqueous solution were determined by potentiometric titrations (25 degrees C, I = 0.1 mol dm(-3) KNO(3)). The results show that protonated aliphatic-substituted L (a,d) and aromatic-substituted L (b,c) ligands and/or Zn(II) ion can efficiently recognition the substrate, ATP. All of the equilibrium studies, (1)H and (31)P nuclear magnetic resonance spectra indicate that multiple interactions, including coordination, pi-stacking, ion-pairing, H-bonding, and possible ion-pi-donor, hydrophobic and even van der Waals interactions exist in the Zn(II)-L-ATP systems. On the other hand, the recognition of the substrates by the protonated ligands was significantly promoted by the addition of Zn(II), which leads to coordination competition between the mixed ligands, L and nucleotide. In Zn(II)/L/ATP systems the tendency for phosphate chain to receive proton and metal ion increases, facilitating the cleavage of the phosphate chain of the nucleotide.
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PMID:Recognition promoted by Zn2+ between phenanthroline bridging polyaza ligands and nucleotides--Zn2+ acts as 'messenger' between the receptor and substrate. 1272 Feb 79

Levinson, Hillel S. (U.S. Army Natick Laboratories, Natick, Mass.), and Mildred T. Hyatt. Effect of sporulation medium on heat resistance, chemical composition, and germination of Bacillus megaterium spores. J. Bacteriol. 87:876-886. 1964.-Bacillus megaterium spores, grown on variously supplemented media, had varying concentrations of P, Ca, Mn, or dipicolinic acid. Supplementation with CaCl(2) yielded spores with increased heat resistance; addition of l-glutamate, l-proline, or increase of the phosphate concentration yielded spores with reduced heat resistance. Germination characteristics depended on both the sporulation medium and the germinant (glucose, l-alanine, l-leucine, or KNO(3)); pronounced differences were demonstrable with glucose and l-alanine, which trigger germination via different metabolic pathways. An increase in CaCl(2) during sporulation yielded spores with increased germination in glucose but not in l-alanine. Germination in l-alanine was optimal with spores produced on media containing 0.1 mm MnCl(2), but germination of such spores was minimal in glucose. An increase in the sporulation medium phosphate decreased the initial germination rate in glucose, but not in l-alanine. Spores produced in CaCl(2)-supplemented media had increased heat-activation requirements (increased dormancy) for germination induced by l-alanine, and decreased heat-shock requirements for glucose-induced germination. An increase of sporulation phosphate yielded spores with reduced dormancy for germination induced by l-alanine, but with unchanged dormancy on the other germinants. Spores produced with added l-glutamate had reduced dormancy for glucose-induced germination, and increased dormancy for germination induced by l-alanine. Addition of CaCl(2) or l-glutamate to the sporulation medium yielded spores with increased sensitivity to "ionic germination" (with KI). Spores from synthetic medium were incapacitated for full postgerminative development, as shown by repression of the changes in oxygen-uptake rate which accompany normal cell division.
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PMID:EFFECT OF SPORULATION MEDIUM ON HEAT RESISTANCE, CHEMICAL COMPOSITION, AND GERMINATION OF BACILLUS MEGATERIUM SPORES. 1413 27

There is no unique formula for angiogenesis. Instead there is a large group of potential participating proteins that interact in complex ways. Depending upon the surrounding cell types and the relative expression levels of angiogenesis-related proteins, the 'angiogenesis cascade' can vary. Therefore, it is valuable to study and compare the role of proteins in several well-characterized vascular beds. The eye provides a useful model system, because it contains several vascular beds sandwiched between avascular tissue. This allows for unequivocal identification and quantitation of new vessels. Retina-specific promoters combined with inducible promoter systems provide a means to regulate the expression of proteins of interest. As a relatively isolated compartment, the eye also provides advantages for gene transfer. By gaining insight regarding the molecular signals involved in various types of ocular angiogenesis, general concepts can emerge that may apply to other settings, including tumor angiogenesis. One concept that has emerged is that despite participation of multiple stimulatory factors for ocular neovascularization, VEGF plays an essential role and interruption of VEGF signaling is an important therapeutic strategy. Another concept is that while most studies have focused on prevention of ocular neovascularization, regression of new vessels is desirable and is achievable with at least three agents, combretastatin A-4 phosphate, pigment epithelium-derived factor, and angiopoietin-2. Finally, endostatin and angiostatin, which have been sources of controversy because of inconsistent results in tumor models, have been shown to have good efficacy when delivered by gene transfer in models of ocular neovascularization. These results provide leads for new ocular treatments and perspective for evaluation of studies of neovascularization in extraocular tissues.
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PMID:Ocular neovascularization: a valuable model system. 1452 78

Naturally occurring angiogenesis inhibitors can inhibit different steps of the angiogenic process, such as endothelial cell migration. However, the mechanisms underlying this inhibition have not been elucidated. We demonstrate that migration of human umbilical vein endothelial cells induced by the potent endothelial cell chemoattractant sphingosine 1-phosphate is refractory to inhibition by well-characterized angiogenesis inhibitors such as endostatin and plasminogen-related protein-B. Our data support the contention that for effective blockage of tumor-induced angiogenesis, antagonists of both G protein-coupled receptor signaling and receptor tyrosine kinase signaling must be combined.
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PMID:Sphingosine 1-phosphate and cell migration: resistance to angiogenesis inhibitors. 1455 Feb 87

Bacillus thuringiensis subsp. medellin is known to produce the Cry11Bb protein of 94 kDa, which is toxic for mosquito larvae due to permeabilization of the plasma membrane of midgut epithelial cells. Earlier we found that a 2.8-kDa novel peptide BTM-P1, which was artificially synthesized taking into account the primary structure of Cry11Bb endotoxin, is active against several species of bacteria. In this work we show that BTM-P1 induces cyclosporin A-insensitive swelling of rat liver mitochondria in various salt solutions but not in the sucrose medium. Inorganic phosphate and Ca(2+) significantly increased this effect of the peptide. The uncoupling action of BTM-P1 on oxidative phosphorylation was stronger in the potassium-containing media and correlated with a decrease of the inner membrane potential of mitochondria. In isotonic KNO(3), KCl, or NH(4)NO(3) media, a complete drop of the inner membrane potential was observed at 1-2 microg/ml of the peptide. The peptide-induced swelling was increased by energization of mitochondria in the potassium-containing media, but it was inhibited in the NaNO(3), NH(4)NO(3), and Tris-NO(3) media. All mitochondrial effects of the peptide were completely prevented by adding a single N-terminal tryptophan residue to the peptide sequence. We suggest a mechanism of membrane permeabilization that includes a transmembrane- and surface potential-dependent insertion of the polycation peptide into the lipid bilayer and its oligomerization leading to formation of ion channels and also to the mitochondrial permeability transition pore opening in a cyclosporin A-insensitive manner.
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PMID:Mitochondria permeabilization by a novel polycation peptide BTM-P1. 1571 82

Recent studies demonstrate low serum levels of 25-hydroxyvitamin D in patients with congestive heart failure (CHF). Although this may in part reflect reduced capacity for outdoor exercise, the possibility that poor vitamin D status increases risk for left ventricular hypertrophy (LVH), and its common sequel CHF, merits consideration. In cardiomyocytes, hormones which activate protein kinase C (PKC) -- including norepinephrine, angiotensin II, and endostatin, implicated in the pathogenesis of LVH -- induce a hypertrophic response analogous to that seen in LVH. Transgenic mice overexpressing PKC-beta2 or its upstream activator Galphaq in cardiac myofibers develop a syndrome similar to LVH. Parathyroid hormone (PTH) also activates Galphaq and PKC in cardiomyocytes, and provokes the expected hypertrophic response. Both primary and secondary hyperparathyroidism are associated with high risk for LVH. Moreover, in uncomplicated essential hypertension, left ventricular mass index has been shown to correlate very tightly with serum PTH levels, independent of blood pressure. This latter finding suggests that variations of PTH within the normal range can influence induction of LVH in at-risk subjects. If so, nutritional and lifestyle measures which modulate PTH secretion may have an impact on LVH risk. PTH secretion should be down-regulated by good vitamin D status -- achieved through supplementation or regular uv exposure -- and by vegan diets moderately low in bioavailable phosphate. Although high calcium intakes can likewise suppress PTH, they also boost renin secretion, which could have a countervailing effect on risk for LVH. Whether these nutritional measures do indeed influence LVH risk could be examined in prospective studies targeting patients at high risk, such as hypertensives.
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PMID:Nutritional modulation of parathyroid hormone secretion may influence risk for left ventricular hypertrophy. 1578 May 3


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