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)

At first glance, the antiangiogenic drug Avastin (bevacizumab) must paradoxically normalize angiogenesis, in order to potentiate chemotherapy. However, this may be only a part of the story. Here I discuss that the synergy between Avastin and chemotherapy is also consistent with the classic notion that antiangiogenic therapy actually inhibits angiogenesis. It has been previously predicted that inhibition of angiogenesis (action) will induce a reactive resistance (reaction), which is mediated by the HIF-1/VEGF pathway in cancer cells, thus allowing both endothelial and cancer cells to resist therapy. Therefore, inhibitors of the reactive resistance are needed to potentiate anti-angiogenic therapy. In the combination of chemotherapy plus Avastin, it is chemotherapy that is the principal antiangiogenic agent. This role of chemotherapy requires that something should be added to block the reaction. And this is exactly what Avastin does (by blocking VEGF). While chemotherapy inhibits angiogenesis, Avastin abrogates the reactive resistance, sensitizing both endothelial and cancer cells to therapy.
Cancer Biol Ther 2005 Dec
PMID:How Avastin potentiates chemotherapeutic drugs: action and reaction in antiangiogenic therapy. 1632 83

The distribution and lignocellulolytic activity of the microbial community was determined on a large log of Douglas fir (Pseudotsuga menziesii) in a Pacific Northwest stream. Scanning electron microscopy, plate counts, and degradation of [C]lignocelluloses prepared from Douglas fir and incubated with samples of wood taken from the surface and within the log revealed that most of the microbial colonization and lignocellulose-degrading activity occurred on the surface. Labeled lignocellulose and surface wood samples were incubated in vitro with nutrient supplements to determine potential limiting factors of [C]lignocellulose degradation. Incubations carried out in a nitrogenless mineral salts and trace elements solution were no more favorable to degradation than those carried out in distilled water alone. Incubations supplemented with either (NH(4))(2)SO(4) or organic nitrogen sources showed large increases in the rates of mineralization over incubations with mineral salts and trace elements alone, with the greatest effect being observed from an addition of (NH(4))(2)SO(4). Subsequent incubations with (NH(4))(2)SO(4), KNO(3), and NH(4)NO(3) revealed that KNO(3) was the most favorable for lignin degradation, whereas all three supplements were equally favorable for cellulose degradation. Supplementation with glucose repressed both lignin and cellulose mineralization. The results reported in this study indicate that nitrogen limitation of wood decomposition may exist in streams of the Pacific Northwest. The radiotracer technique was shown to be a sensitive and useful tool for assessing relative patterns of lignocellulose decay and microbial activity in wood, along with the importance of thoroughly characterizing the experimental system before its general acceptance.
Appl Environ Microbiol 1983 Dec
PMID:Microbial decomposition of wood in streams: distribution of microflora and factors affecting [C]lignocellulose mineralization. 1634 48

Treatment options for advanced colorectal have improved substantially in recent years as a number of agents have been developed that have different targets and mechanisms of action. Significant improvements in outcomes have been observed by combining multiple chemotherapeutic agents instead of the single-agent approach. Some debate still remains regarding which combination is most effective and in what order regimens should be given. In addition to cytotoxic chemotherapy drugs, targeted biologic agents have been developed to inhibit tumor angiogenesis, which may hamper the viability of the tumor. There may also be a synergistic effect between antiangiogenic agents and chemotherapy. Regulation of tumor angiogenesis may actually improve blood flow throughout the tumor, which could enhance delivery of chemotherapy through the circulation. One antiangiogenic agent currently approved for the treatment of advanced colorectal cancer is bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, a ligand known to be important for angiogenesis. The other currently approved biologic agent, cetuximab, targets the epidermal growth factor receptor. The combination of bevacizumab plus cetuximab has a biologic rationale. Randomized trials incorporating combination chemotherapy regimens plus both bevacizumab and cetuximab are currently underway, as are preliminary studies withnovel angiogenesis inhibitors.
Clin Adv Hematol Oncol 2005 Dec
PMID:Angiogenesis inhibition in the treatment of colorectal cancer Part 3 of a 3-part series: targeting VEGF--current and future research directions. 1655 33

The optimum in vivo nitrate reductase (NR) assay medium for soybean (Glycine max [L.] Merr.) leaves was 50 mm KNO(3), 1% (v/v) 1- propanol, and 100 mm potassium phosphate buffer (pH 7.5).Loss of in vivo NR activity from leaves of soybeans exposed to dark was fastest at 40 C and slowest at 20 C. However, by the end of a 16-hr dark period, even those plants exposed to the lowest (20 C) temperature had lost 95% of the initial activity. Upon re-exposure to light, following a 16 hr-30 C dark period, in vivo NR activity increased rapidly to maximum levels after 4 hr light. The rate of increase was proportional to light intensity (6, 16, and 45 klux) and independent of temperature (20, 30, and 40 C).Studies with field-grown soybeans indicated that mighttime temperature (16-27 C) had no effect on the subsequent in vivo NR activity in sunlight at ambient temperature. There was a marked decrease in in vivo NR activity in late afternoon with the field-grown plants. This decrease continued throughout the night with elevated temperature (27 C) while NR activity increased when a cooler (16 C) night temperature was imposed.The changes in in vivo NR activity in response to light and dark treatments were quite rapid and thought to be related to energy limitations as well as enzyme level.
Plant Physiol 1976 Dec
PMID:Nitrate Reductase Activity in Soybeans (Glycine max [L.] Merr.): I. Effects of Light and Temperature. 1665 55

Pisum sativum L. cv. Trapper plants were inoculated and grown in a controlled environment on N-free nutrient solution. After 4 weeks N was supplied to treatment plants as NH(4)NO(3), KNO(3), or NH(4)Cl and rates of C(2)H(2) reduction, root + nodule respiration, and leaf photosynthesis were determined 1 week later. The increase in respiration per unit of C(2)H(2) reduction was not affected by either the form of N added or the light conditions during growth, although the basal respiration rate with no C(2)H(2) reduction increased with irradiance level. The mean regression coefficient from plots of respiration versus C(2)H(2) reduction was 0.23 + 0.04 (P [unk] .01) mg of CO(2) (mumol of C(2)H(2) reduced)(-1) which was very similar to the value for the coefficient of respiration associated with nitrogenase activity estimated by subtracting growth and maintenance respiration. Since the rate of N accumulation in N-free nutrient conditions was proportional to the rate of C(2)H(2) reduction, it appears that the method gives a true estimate of the energy requirements for N fixation which for these conditions was equivalent to 17 grams of carbohydrate consumed per gram of N fixed.
Plant Physiol 1977 Dec
PMID:Respiration and the energy requirement for nitrogen fixation in nodulated pea roots. 1666 Jan 92

The commercial tomato, lycopersicon esculentum Mill. cv Walter, and its wild relative, Lycopersicon cheesmanii ssp. minor (Hook.) C.H. Mull., were grown for 30 days under controlled conditions and in solution culture varying in its content of Na(+) and K(+). Subsequently, (86)Rb-labeled K(+) uptake and distribution were studied. From all solutions, ;Walter' consistently absorbed (86)Rb-labeled K(+) at a higher rate in micromoles per gram fresh weight per 30 minutes than L. cheesmanii. L. cheesmanii distributed a greater proportion of the absorbed K(+) from its root to its shoot. When 0.6 millimolar NaNO(3) replaced 0.6 millimolar KNO(3) in the pretreatment solution, intact plants of both genotypes followed a similar pattern as when they were pretreated with K(+) only, but a greater percentage of the absorbed K(+) remained in the roots. Leaf slices of L. cheesmanii plants deprived of K(+) for 6 days showed a greater rate of K(+) uptake than did slices from ;Walter' plants pretreated the same way. Stem slices of L. cheesmanii, however, had a lower uptake rate than did those of ;Walter'. Both leaf and stem slices of ;Walter' plants, pretreated 6 days with 0.6 millimolar NaNO(3) substituting for 0.6 millimolar KNO(3) in their growth medium, had greater rates of (86)Rb-labeled K(+) uptake from 0.5 and 20 millimolar KCl solutions than did slices of L. cheesmanii. These marked differences in patterns of ion uptake and translocation indicate that these genotypes of tomato have evolved different mechanisms to deal with K(+) and Na(+) in their environments.
Plant Physiol 1985 Dec
PMID:Potassium transport in two tomato species : lycopersicon esculentum and lycopersicon cheesmanii. 1666 31

The effects of tabtoxinine-beta-lactam (T-beta-L) on nitrate uptake and glutamine synthetase (GS) and nitrate reductase (NR) activities in roots of Avena sativa seedlings were determined. Seven-day-old oat seedlings placed in a 10 mm KNO(3) and 0.5 mm T-beta-L solution for 24 hours took up T-beta-L and lost approximately 90% of their root GS activity. [(3)H]-T-beta-L taken up by roots of seven-day-old oat seedlings was associated with GS immunoprecipitated from the extract of these roots. Total nitrate uptake and in vivo NR activity were decreased approximately 50% in the T-beta-L treated roots. However, T-beta-L uptake did not affect the induction phases of nitrate uptake or reduction, nor did it inhibit in vitro NR activity. Thus, the decrease in nitrate uptake and reduction is a secondary effect of T-beta-L action. Roots of seven-day-old oat seedlings were inoculated with Pseudomonas syringae pv tabaci (Tox+) and the pathogen population in the rhizosphere was estimated by dilution plate count; 6 x 10(13) bacteria were recovered after 3 days, as compared to the original inoculation with 7 x 10(9) bacteria, indicating a significant growth of the pathogen in the rhizosphere. The bacteria recovered from the rhizosphere caused chlorosis in tobacco leaves and produced T-beta-L in culture; 1 x 10(14) bacteria were recovered from roots of seedlings inoculated with P. syringae pv tabaci (Tox-) using the same inoculation and assay procedure as for the pv tabaci (Tox+). Extracts of surface-sterilized roots previously inoculated with P. syringae pv tabaci (Tox+) did not produce viable bacterial cultures when plated out on a complete medium. Oat seedlings growing in sand culture and inoculated with P. syringae pv tabaci (Tox+) had developed chlorosis, and root GS activity had declined to less than 10% of controls after 3 days. Conversely, seedlings inoculated with P. syringae pv tabaci (Tox-) never developed chlorosis and maintained normal levels of GS activity. All oat plants inoculated with P. syringae pv tabaci (Tox+) died within 7 days after inoculation as compared to the plants inoculated with P. syringae pv tabaci (Tox-) which grew to maturity.
Plant Physiol 1986 Dec
PMID:Effects of Tabtoxinine-beta-Lactam on Nitrogen Metabolism in Avena sativa L. Roots. 1666 33

Thalli discs of the marine macroalga Ulva lactuca were given inorganic carbon in the form of HCO(3) (-), and the progression of photosynthetic O(2) evolution was followed and compared with predicted O(2) evolution as based on calculated external formation of CO(2) (extracellular carbonic anhydrase was not present in this species) and its carboxylation (according to the K(m)(CO(2)) of ribulose-1,5-bisphosphate carboxylase/oxygenase), at two different pHs, assuming a photosynthetic quotient of 1. The K(m)(inorganic carbon) was some 2.5 times lower at pH 5.6 than at the natural seawater pH of 8.2, whereas V(max) was similar under the two conditions, indicating that the unnaturally low pH per se had no adverse effect on U. lactuca's photosynthetic performance. These results, therefore, could be evaluated with regard to differential CO(2) and HCO(3) (-) utilization. The photosynthetic performance observed at the lower pH largely followed that predicted, with a slight discrepancy probably reflecting a minor diffusion barrier to CO(2) uptake. At pH 8.2, however, dehydration rates were too slow to supply CO(2) for the measured photosynthetic response. Given the absence of external carbonic anhydrase activity, this finding supports the view that HCO(3) (-) transport provides higher than external concentrations of CO(2) at the ribulose-1,5-bisphosphate carboxylase/oxygenase site. Uptake of HCO(3) (-) by U. lactuca was further indicated by the effects of potential inhibitors at pH 8.2. The alleged band 3 membrane anion exchange protein inhibitor 4,4'-diisothiocyanostilbene-2,2'disulphonate reduced photosynthetic rates only when HCO(3) (-) (but not CO(2)) could be the extracellular inorganic carbon form taken up. A similar, but less drastic, HCO(3) (-)-competitive inhibition of photosynthesis was obtained with Kl and KNO(3). It is suggested that, under ambient conditions, HCO(3) (-) is transported into cells at defined sites either via facilitated diffusion or active uptake, and that such transport is the basis for elevated internal [CO(2)] at the site of ribulose-1,5-bisphosphate carboxylase/oxygenase carboxylation.
Plant Physiol 1991 Dec
PMID:Utilization of Inorganic Carbon by Ulva lactuca. 1666 69

Phosphoenolpyruvate carboxylase (PEPcase) activity was studied in excised leaves of wheat (Triticum aestivum L.) in the dark and in the light, in presence of either N-free (low-NO(3) (-) leaves) or 40 millimolar KNO(3) (high-NO(3) (-) leaves) nutrient solutions. PEPcase activity increased to 2.7-fold higher than that measured in dark-adapted tissue (control) during the first 60 minutes and continued to increase more slowly to 3.8-fold that of the control. This level was reached after 200 minutes exposure of the leaves to light and high NO(3) (-). In contrast, the lower rate of increase recorded for low-NO(3) (-) leaves ceased after 60 minutes of exposure to light at 2.3-fold the control level. The short-term NO(3) (-) effect increased linearly with the level of NO(3) (-) uptake. In immunoprecipitation experiments, the antibody concentration for PEPcase precipitation increased with the protein extracts from the different treatments in the order: control, illuminated low-NO(3) (-) leaves, illuminated high-NO(3) (-) leaves. This order also applied with regard to a decreasing sensitivity to malate and an increasing stimulation by okadaic acid (an inhibitor of P-protein phosphatases). Following these studies, (32)P labeling experiments were carried out in vivo. These showed that the light-induced change in the properties of the PEPcase was due to an alteration in the phosphorylation state of the protein and that this effect was enhanced in high-NO(3) (-) conditions. Based on the responses of PEPcase and sucrose phosphate synthase in wheat leaves to light and NO(3) (-), an interpretation of the role of NO(3) (-) as either an inhibitor of P-protein phosphatase(s) or activator of protein kinase(s) is inferred. In the presence of NO(3) (-), the phosphorylation state of both PEPcase and sucrose phosphate synthase is increased. This causes activation of the former enzyme and inhibition of the latter. We suggest that NO(3) (-) modulates the relative protein kinase/protein phosphatase ratio to favor increased phosphorylation of both enzymes in order to redirect carbon flow away from sucrose synthesis and toward amino acid synthesis.
Plant Physiol 1991 Dec
PMID:Effect of Light and NO(3) on Wheat Leaf Phosphoenolpyruvate Carboxylase Activity: Evidence for Covalent Modulation of the C(3) Enzyme. 1666 73

We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin, on the occurrence of sporadic breast cancer in 181 patients and 448 controls. The homozygous 104NN polymorphism was found in five patients but was absent in controls (2.8% vs 0.0%; P = 0.002). Individuals with this genotype had a significantly increased risk for disease. Our results suggest, for the first time, that the homozygous 104NN polymorphism, even at low frequency, constitutes an important inherited determinant of the disease.
Breast Cancer Res Treat 2006 Dec
PMID:A high risk of occurrence of sporadic breast cancer in individuals with the 104NN polymorphism of the COL18A1 gene. 1680 76


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