1,720,987 research outputs found
Following the tracks of AKT1 gene
No full textThe AKT or PKB family of protein kinases is one of the best characterized targets of phosphoinositide 3-kinases or PI3Ks. The AKT/PKB signal transduction pathway regulates many growth and survival mechanisms including transcription, cell cycle progression, metabolism, apoptosis, invasion and metastasis. Recently, Carpten et al. (Nature 2007;448:439-44) reported a very interesting study on the isoform AKT1 (PKBalpha). They described a novel point mutation (E17K) in the pleckstrin homology domain (PHD) of the AKT1 gene in human breast, colorectal and ovarian cancers, and demonstrated that it induces leukemia in mice. Here we give a critical appraisal of this finding and underline its clinical impact. We also discuss possible interventions for therapeutic development of AKT inhibitors to treat human cancer
Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis
No full textGastric cancer is a common aggressive malignancy. Although its incidence shows considerable variation among different countries, gastric cancer is still a major health problem worldwide. The causes of stomach cancer are not completely understood. What is clear is that gastric cancer is a multi-stage process involving genetic and epigenetic factors. This review is an in-depth study of the known genetic and epigenetic processes in the development of this tumor, and delineates possible approaches in gene and epigenetic therapy
How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data, reflections and reactions
No full textRUNX3 is the oldest known gene in the RUNX family. Data have demonstrated its function to be thoroughly involved the neurogenesis of the dorsal root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium. As a TGF-beta target, RUNX3 protein is believed to be involved in TGF-beta-mediated tumor suppressor pathway; however, little is known about its role in apoptosis. According to recent data reported by Yamamura et al., (J Biol Chem 2006; 281:5267-76), RUNX3 interacts with FoxO3a/FKHRL1 expressed in gastric cancer cells to activate Bim and induce apoptosis. The cooperation between RUNX3 and the PI3K/Akt signaling pathway component FoxO3a/FKHRL1 suggests the putative role of RUNX3 in the homoeostasis of gastric cells and in stomach cancer control. Here we discuss recent breakthroughs in our understanding of the mechanisms of RUNX3 in gastric malignancy and comment on possible future trends and perspectives
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
Potential Pathophysiological Mechanisms of the Beneficial Role of Endometrial Injury in In Vitro Fertilization Outcome
No full textSuccessful embryo implantation is a complex process that involves multiple biological mechanisms and reciprocal interactions between the embryo and the proliferated endometrium. In this review, we provide an informative contribution on the pathways underlying the beneficial nature of endometrial injury toward improving implantation rates of embryos conceived and through in vitro fertilization. The evidence published to date are in favor of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained and recurrent implantation failure. Endometrial injury triggers a series of biological responses but the findings suggest that no particular pathway is solely adequate to explain the association between trauma and improved pregnancy rates rather than a cluster of events in response to trauma which benefits embryo implantation in ways both known and unknown to the scientific communit
Helicobacter pylori as a class I carcinogen: Physiopathology and management strategies
No full textThe gram-negative bacterium Helicobacter pylori is known as a persistent colonizer of the human stomach, and probably less known is that it is also involved in extraintestinal diseases. Public awareness of its contribution in the development of gastric cancer is less than 15 years old. The efficacy of the current therapies based on antibiotics against H. pylori has been limited by difficulties such as antibiotic resistance and recurrence. As a consequence, the development of promising vaccines was prompted as the best preventive measure. Unfortunately, so far vaccines failed the transition from animal models to human trials. This keynote presentation is to provide a bird's eye view of H. pylori-related gastric diseases, including gastric cancer, with a synthesis of the molecular mechanisms involved, and an exhaustive presentation and discussion of the current therapeutic guidelines and future strategies for prevention or therapy
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
Transvaginal ovarian trauma, poor responders and improvement of success rates in IVF: Anecdotal data and a hypothesis
No full textIn this report, we propose an intervention capable of improving IVF outcomes in subfertile women with poor ovarian response. This intervention derives from anecdotal data and observations in our daily practice, but most importantly from trials on experimental models and subfertile women with Polycystic Ovarian Syndrome (PCOS). Our hypothesis suggests that transvaginal induction of trauma to the ovary in the cycle preceding IVF should benefit poor ovarian responders and their lowered pregnancy rates by increasing - at least - the number of retrieved oocytes during oocyte retrieval. Up-to-the minute data show that, via this means, there is a unique response of the ovarian surface epithelium and stroma to the induced trauma. The potential pathways of this beneficial response involve an improvement of the raised gonadotrophins to act either through the mechanical reduction of the size of the ovary or through alterations of the hormonal profile by lowering LH, inhibin and local androgen concentrations through hypothalamic-pituitary axis feedbacks, the induction of increased blood flow to the ovaries, a differentiated local immune reaction and a non-elucidated as yet role of reactive oxygen species. In this report, we also describe the technique and the associated possible negative points while we try to point out the needed research steps to ensure its efficiency before it enters daily clinical practic
Review: MicroRNAs in assisted reproduction and their potential role in IVF failure
No full textMicroRNAs (miRNAs) have recently emerged as important regulators of gene
expression stability. In the endometrium, miRNAs are involved in the dynamic
changes associated with the menstrual cycle, implicated in implantation and in
reproductive disorders. We performed a review in an attempt to assess the
potential biological pathways linking altered miRNAs profiles with in vitro
fertilisation (IVF) failure. Crucially, as miRNAs appear to have a significant
role in the course of reproduction, they are excellent research candidates with
the potential to enable a better understanding over the underlying molecular
activities that prevent implantation and further progression of the embryo.
Further steps include in-depth pathway mapping of the implantation process and
the characterization of the respective miRNAs and associated links. The
efficiency of any intervention should determine whether miRNA profiling could
possibly be adopted in routine practice to substantially improve the diagnostic
accuracy and, in parallel, the directed treatment of the next-generation IVF
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