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Promoting Effects (promoting + effects)
Selected AbstractsGene expression analysis of BCR/ABL1-dependent transcriptional response reveals enrichment for genes involved in negative feedback regulationGENES, CHROMOSOMES AND CANCER, Issue 4 2008Petra Håkansson Philadelphia (Ph) chromosome-positive leukemia is characterized by the BCR/ABL1 fusion protein that affects a wide range of signal transduction pathways. The knowledge about its downstream target genes is, however, still quite limited. To identify novel BCR/ABL1-regulated genes we used global gene expression profiling of several Ph-positive and Ph-negative cell lines treated with imatinib. Following imatinib treatment, the Ph-positive cells showed decreased growth, viability, and reduced phosphorylation of BCR/ABL1 and STAT5. In total, 142 genes were identified as being dependent on BCR/ABL1-mediated signaling, mainly including genes involved in signal transduction, e.g. the JAK/STAT, MAPK, TGFB, and insulin signaling pathways, and in regulation of metabolism. Interestingly, BCR/ABL1 was found to activate several genes involved in negative feedback regulation (CISH, SOCS2, SOCS3, PIM1, DUSP6, and TNFAIP3), which may act to indirectly suppress the tumor promoting effects exerted by BCR/ABL1. In addition, several genes identified as deregulated upon BCR/ABL1 expression could be assigned to the TGFB and NFkB signaling pathways, as well as to reflect the metabolic adjustments needed for rapidly growing cells. Apart from providing important pathogenetic insights into BCR/ABL1 -mediated leukemogenesis, the present study also provides a number of pathways/individual genes that may provide attractive targets for future development of targeted therapies. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045,2257/suppmat. © 2008 Wiley-Liss, Inc. [source] Approaches to measuring the effects of wake-promoting drugs: a focus on cognitive functionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2009Christopher J. Edgar Abstract Objectives In clinical drug development, wakefulness and wake-promotion may be assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake-promoting drugs may have nootropic properties (and vice versa). Clinical trials of wake-promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake-promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have underexplored or unknown wake promoting properties. Copyright © 2009 John Wiley & Sons, Ltd. [source] Growth promoting effects of human placental lactogen during early organogenesis: a link to insulin-like growth factorsJOURNAL OF ANATOMY, Issue 6 2001AHMET KAGAN KARABULUT Many maternally derived factors may be involved in the regulation of embryonic growth but the control mechanisms involved are poorly understood. Human placental lactogen (hPL) has been implicated in playing a role in the control of embryonic growth. Several investigators suggested that there may be a possible link between the effects of this hormone and insulin-like growth factors (IGFs). In order to determine the growth promoting potential of hPL and involvement of IGFs in the mechanism of action of the hormone, 9.5 d rat embryos were cultured in vitro for 48 h in depleted serum in the presence and absence of hPL with additional IGF antisera. The growth supporting capacity of the serum was reduced by removal of low molecular weight molecules by prolonged filtration of the serum using filters with a molecular weight exclusion of 30 kDa. Addition of hPL (3.2,25.6 ng/ml) to depleted serum significantly improved embryonic growth and development, suggesting that the developing embryo may utilise hPL. The presence of antisera against hPL, IGF-I and -II abolished the hPL-induced increase in the development in all parameters suggesting that there may be a possible link between the IGFs and the effects of hPL on rat embryonic development and this hormone may achieve its growth promoting effects via IGFs. [source] Weaning pig performance and faecal microbiota with and without in-feed addition of rare earth elementsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 9-10 2006M. Kraatz Summary Two 6-week feeding trials were conducted on a total of 112 newly weaned piglets to examine the recently reported growth promoting effects of dietary rare earth elements (REE) in European pig production. Rare earth element-diets were supplemented with a REE-citrate premix of lanthanum and the light lanthanoides cerium, praseodymium and neodymium at 200 mg/kg for 6 weeks after weaning. Overall for both trials, growth performance of REE-citrate and control fed piglets did not differ significantly (p > 0.05). An early enhancive tendency for REE-citrate in trial 1 (feed conversion ratio, FCR ,3%, p = 0.15) proved irreproducible in trial 2. In the late period of trial 1, in-feed addition of REE-citrate significantly impaired piglet performance (FCR + 8%, p =0.01). A cultivation-independent molecular approach, polymerase chain reaction-denaturing gradient gel electrophoresis was further applied to assess REE induced alterations in the predominant faecal microbiota from weaning pigs. Calculation of various ecological characteristics does not indicate (p > 0.05) an often discussed selective effect on local microbial composition of dietary REE. [source] Type II nitric oxide synthase (NOS2) expression correlates with lymph node status in oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2001Peter A. Brennan Abstract: In tumour biology, nitric oxide (NO) has a complex array of concentration-dependent actions, including both inhibitory and promoting effects. It is thought that the levels of NO found in many human cancers lead to enhanced angiogenesis and tumour dissemination. In the current study, we assessed the immunohistochemical expression of the enzyme type II nitric oxide synthase (NOS2) in 41 cases of oral squamous cell carcinoma and correlated the findings with lymph node status. A significant relationship was found between NOS2 expression and lymph node metastasis (P<0.0002). Furthermore, lymph node metastasis correlated with the degree and intensity of staining seen (P<0.001). No correlation was found between the size of the primary tumour, degree of tumour differentiation or smoking status and NOS2 staining. Western blotting confirmed NOS2 protein expression in select cases. As with many other human tumours, NOS2 is not a ubiquitous finding in oral cancer. Its expression may be of value in assessing lymph node status prior to surgery, and it represents a target for possible therapeutic manipulation. [source] Role of Wake-Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep-Promoting Effects of EthanolALCOHOLISM, Issue 6 2010Mahesh M. Thakkar Background:, Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake-promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol-induced sleep associated with the inhibition of the BF wake-promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep-promoting effects of ethanol? Methods:, To address these questions, we performed 3 experiments in Sprague,Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c-Fos expression (a marker of neuronal activation) in the BF wake-promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol-induced sleep. Results:, Significant increase in non-rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine into the BF significantly attenuated sleep-promoting effects of ethanol. Conclusion:, These results suggest that the inhibition of BF wake-promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol. [source] Hibiscus polyphenol-rich extract induces apoptosis in human gastric carcinoma cells via p53 phosphorylation and p38 MAPK/FasL cascade pathwayMOLECULAR CARCINOGENESIS, Issue 2 2005Hui-Hsuan Lin Abstract In view of the continuing need for effective anticancer agents, and the association of diet with reduced cancer risk, edible plants are increasingly being considered as sources of anticancer drugs. Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Polyphenols had been demonstrated previously to possess antioxidative and antitumor promoting effects. In this study, investigations were conducted to examine the mechanism of the anticancer activity of H. sabdariffa L., Hibiscus polyphenol-rich extracts (HPE). Using HPLC assay, HPE was demonstrated to contain various polyphenols. HPE induced cell death of eight kinds of cell lines in a concentration-dependent manner. Among them human gastric carcinoma (AGS) cells were the most susceptible to HPE (0.95 mg/mL HPE inhibited its growth by 50%). Our results revealed that AGS cells underwent DNA fragmentation, and had an increase in the distribution of hypodiploid phase (apoptotic peak, 52.36%) after a 24-h treatment with HPE (2.0 mg/mL). This effect of HPE in AGS cells might be mediated via p53 signaling and p38 MAPK/FasL cascade pathway, as demonstrated by an increase in the phosphorylation of p53 and the usage of a specific p38 inhibitor, SB203580. Thus, our data present the first evidence of HPE as an apoptosis inducer in AGS cells and these findings may open interesting perspectives to the strategy in human gastric cancer treatment. © 2005 Wiley-Liss, Inc. [source] Resveratrol attenuates 1,2-dimethylhydrazine (DMH) induced glycoconjugate abnormalities during various stages of colon carcinogenesisPHYTOTHERAPY RESEARCH, Issue 8 2009Murugan Sengottuvelan Abstract Although a myriad of health promoting effects has been attributed to resveratrol (Res) (3,5,4,-trihydroxy- trans -stilbene), a phytoalexin, the most interesting is its anticancer property. The aim of this work was to elucidate the effectiveness of Res against cellular transformation (glycoconjugate alterations) initiated by 1,2-dimethylhydrazine (DMH), a colon specific carcinogen. Group 1 were control rats, group 2 were control rats that received Res (8 mg/kg body weight orally every day), rats in groups 3,6 were treated weekly with DMH (20 mg/kg body weight, subcutaneously × 15 times). In addition, groups 4,6 received Res (as in group 2) in three dietary regimens: initiation (I), post-initiation (PI) and entire period (EP). At the end of the 30 week experimental period in DMH alone exposed rats, altered levels of glycoconjugates (total hexoses, fucose, hexosamine and sialic acid) were observed in liver, intestine and colon tissues. Of the three dietary regimens of Res, the entire period supplementation significantly (p < 0.01) modulated the levels of glycoconjugates and reduced the incidence of adenoma and adenocarcinoma. These findings suggest that Res may extend its chemopreventive effect by restoring the alteration in glycoconjugates that are thought to be involved in the colonic malignant transformation process in this experimental model. Copyright © 2009 John Wiley & Sons, Ltd. [source] Human lactoferrin stimulates skin keratinocyte function and wound re-epithelializationBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2010L. Tang Summary Background, Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. Objectives, To study the potential role of hLF in wound re-epithelialization. Materials and methods, The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Results, Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12- O -tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Conclusions, Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing. 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