1,721,052 research outputs found
Muscarinic receptors and cancer: possible implication in tumor of the nervous system.
No full textMuscarinic receptors are expressed in several primary and metastatic tumours. In some of these, acetylcholine synthesized by the tumour cells through autocrine mechanism often mediated by muscarinic receptors, can contribute to tumour progression, modulating cell proliferation, survival, migration and angiogenesis. Acetylcholine also appears to be involved in brain tumours. In fact, patients with these pathologies show altered levels of ACh in their cerebrospinal fluid. Astrocytomas, glioblastomas and neuroblastomas express both nicotinic and muscarinic receptors, and their activation enhances different signal transduction pathways involving AKT, PIK3, MAPK and ERK. The present review is focused on recent studies demonstrating the muscarinic receptor involvement in the modulation of proliferation, survival and migration in tumours of the central and peripheral nervous system. These data together with observations reported for other pathologies, open up new interesting therapeutic perspectives for ACh and its receptors
The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin.
No full textRecent studies are reviewed indicating that the transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGF?1, PTEN, p53 and fibronectin. The downstream pathways of these factors display multiple nodes of interaction with each other suggesting the existence of a functional network of suppressor factors that serves to maintain normal growth regulation and resist the emergence of transformed variants. Paradoxically, Egr-1 is oncogenic in prostate cancer. In the majority of these cancers PTEN and/or p53 is inactive. It is suggested that these defects in the tumor suppressor network allow for the unopposed induction of TGF?1 and fibronectin, which favor transformation and survival of prostate tumor epithelial cells, explain the role of Egr1 in prostate cancer. Egr1 is a novel and logical target for intervention by gene therapy methods and targeting methods are discussed. Keyword
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Overexpression of uvomorulin in a compaction-negative F9 mutant cell line.
No full textThe mutant F9 cell line F9att-5.51 synthesizes reduced amounts of uvomorulin (UM) protein and we hypothesized earlier (Adamson, Baribault, and Kemler, Dev. Biol. (1990), 138, 338) that this may account for its inability to compact into tightly aggregated balls of cells. Subsequently, when 5.51 cells are treated with retinoic acid to stimulate their differentiation, they are unable to form embryoid bodies as do wild-type cells which form an outer epithelial layer of visceral endoderm cells. We have now examined the possibility that the UM protein made in the mutant line is defective, but find that it is normal in structure and stability. The gene coding for UM appears to be normal as does the mRNA which is synthesized at a normal rate but is severely reduced in steady-state measurements of mutant cells. A rescue experiment was performed by increasing levels of UM in mutant cells by means of transfection with a UM expression vector. The resulting cells expressed abundant UM mRNA and protein but were still unable to form compacted aggregates and did not differentiate into embryoid bodies. Interestingly, the stability of endogenous UM mRNA was improved in the presence of exogenous UM; therefore, a positive feedback mechanism contributes to low mRNA levels in mutant cells. The accumulated data suggest that UM in 5.51 cells is unable to mount a compaction activity because a distal connecting link in the multicomponent process initiated by UM is missing or or aberrant. The missing component is likely to connect UM to actin and the cytoskeleton of the cell
MULTIPLE K-RAS AT CODONS 13,15 AND 19 IN AN AGGRESIVE COLON CANCER CASE REPORT
No full textPOSTER P30
Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice
No full textEarly growth response-1 one gene (Egr-1), one of the immediate early response genes, plays an important role in the adaptive response of the myocardium to hypertrophic stimuli. We aimed to investigate the effects of Egr-1 deletion on cardiac function. Egr-1 knock-out (Egr-1(-/-)) homozygous mice were employed to evaluate the electrophysiological and molecular properties of left ventricular cardiomyocytes (VCM) by using patch-clamp technique, intracellular calcium measurements, real-time PCR, and Western blot. Action potential was prolonged and diastolic potential was positive-shifted in VCMs isolated from Egr-1(-/-) mice, in comparison with those from their wild-type (WT) littermates. The calcium content of the sarcoplasmic reticulum was reduced and the decay time for steady-state calcium transient slowed down. Serca2, Ryr, L-type Ca(2+)-channel, and PLB mRNA expression were reduced in Egr-1(-/-) mice compared with the controls. Moreover, Serca2 protein was reduced, while the amount of Ncx1 protein was increased in Egr-1(-/-) hearts compared with those of the WT littermates. Furthermore, genes involved in heart development (GATA-4, TGF-β) and in Egr-1 regulation (Nab1, Nab2) were down regulated in Egr-1(-/-) mice. These results suggest that Egr-1 plays a pivotal role in regulating excitation-contraction coupling in cardiac myocytes
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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