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Significant Modulation (significant + modulation)
Selected Abstracts,-Microseminoprotein-related molecules may participate in formation of the mesoderm in the chick embryoDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2003Aditi Karandikar It has previously been shown that human ,-microseminoprotein enhances development of mesodermal structures in the chick embryo. The present study was carried out to elucidate the mechanism of action of human ,-microseminoprotein in the chick embryo. ,-Microseminoprotein brought about significant modulation of expression of Brachyury in gastrulating embryos. In approximately 50% of the treated embryos, Brachyury expression was enhanced around the Hensen's node. These cells not only expressed higher levels of Brachyury, but also appeared to switch off Brachyury expression prematurely, postinvagination. The spatial modulation of Brachyury is not clearly reflected in the northern blots, indicating that ,-microseminoprotein treatment results in redistribution of available transcripts or that the upregulation is compensated for by early switching off of Brachyury postinvagination. Because higher levels of Brachyury during gastrulation are believed to result in early exit of cells from the primitive streak, ,-microseminoprotein treatment appeared to have stimulated morphogenetic movements by upregulating Brachyury around the Hensen's node. This deduction was confirmed by scanning electron microscopic analysis that showed that altered morphogenetic movements accompany modulation of Brachyury. The specific responses elicited by ,-microseminoprotein indicate presence of a structurally related molecule in the chick. By western blotting, similar molecules were indeed detected in the chicken seminal plasma and in chick embryos. These data strongly suggest that ,-microseminoprotein-related molecule(s) participates in mesoderm formation in the chick embryo. [source] Embryonic stem cells produce neurotrophins in response to cerebral tissue extract: Cell line-dependent differencesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2007Kristine Bentz Abstract In the present study, we compare the capacity of two different embryonic stem (ES) cell lines to secrete neurotrophins in response to cerebral tissue extract derived from healthy or injured rat brains. The intrinsic capacity of the embryonic cell lines BAC7 (feeder cell-dependent cultivation) to release brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) exceeded the release of these factors by CGR8 cells (feeder cell-free growth) by factors of 10 and 4, respectively. Nerve growth factor (NGF) was secreted only by BAC7 cells. Conditioning of cell lines with cerebral tissue extract derived from healthy or fluid percussion-injured rat brains resulted in a significant time-dependent increase in BDNF release in both cell lines. The increase in BDNF release by BAC7 cells was more pronounced when cells were incubated with brain extract derived from injured brain. However, differences in neurotrophin release associated with the origin of brain extract were at no time statistically significant. Neutrophin-3 and NGF release was inhibited when cell lines were exposed to cerebral tissue extract. The magnitude of the response to cerebral tissue extract was dependent on the intrinsic capacity of the cell lines to release neurotrophins. Our results clearly demonstrate significant variations in the intrinsic capability of different stem cell lines to produce neurotrophic factors. Furthermore, a significant modulation of neurotrophic factor release was observed following conditioning of cell lines with tissue extract derived from rat brains. A significant modulation of neurotrophin release dependent on the source of cerebral tissue extract used was not observed. © 2007 Wiley-Liss, Inc. [source] Determinants of sensitivity and resistance to gemcitabine: The roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancerCANCER SCIENCE, Issue 9 2004Hiroyuki Achiwa Gemcitabine is one of the most commonly used agents for lung cancer chemotherapy, but the determinants of sensitivity and/or resistance to this agent are not yet fully understood. In this study we used quantitative RT-PCR to examine the expression levels of human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK) genes in non-small cell lung cancer (NSCLC) cell lines in relation to sensitivity and resistance to gemcitabine. The basal expression levels of hENT1 were significantly correlated with the IC50 values for gemcitabine (r=-0.6769, P=0.0005), whereas dCK expression levels were not. In a highly gemcitabine-sensitive cell line, NCI-H23, the sensitivity to gemcitabine was inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), an inhibitor of hENT1, without significant modulation of hENT1 expression. These data suggest that hENT1 is associated with gemcitabine sensitivity in lung cancer. We also continuously exposed NCI-H23 cells to gemcitabine and subsequently established the drug-resistant clone H23/GEM-R, which showed a significant decrease of dCK expression; however, hENT1 expression was not altered in the continuously exposed sublines or in the resistant clone. We conclude that increased hENT1 expression is a determinant of gemcitabine sensitivity, while decreased dCK expression is associated with acquired resistance to gemcitabine in NSCLC cells. Thus, hENT1 and dCK might be useful as predictive markers for efficacy of gemcitabine therapy in NSCLC. [source] Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Anna Solovey Activation of the coagulation system is a characteristic feature of sickle cell anemia, which also includes clinical thrombosis. The sickle transgenic mouse abnormally expresses tissue factor (TF) on the pulmonary vein endothelium. Knowing that this aberrancy is stimulated by inflammation, we sought to determine whether nitric oxide (NO) contributes to regulation of endothelial TF expression in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low-TF to high-TF phenotype switch on exposure to hypoxia/reoxygenation. Manipulations of NO biology, such as breathing NO or addition of arginine or L -NAME (N -nitro- L -arginine-methyl-ester) to the diet, caused significant modulations of TF expression. This was also seen in hBERK1 sickle mice, which have a different genetic background and already have high-TF even at ambient air. Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase (eNOS; eNOS-Tg) or to have an eNOS knockout state (one eNOS,/, animal and several eNOS+/, animals) demonstrated that eNOS modulates endothelial TF expression in vivo by down-regulating it. Thus, the biodeficiency of NO characteristic of patients with sickle cell anemia may heighten risk for activation of the coagulation system. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||