1,721,043 research outputs found
Na+-H+ Exchanger, pH Regulation and Cancer.
No full textCancer cells and tissues, regardless of their origin and genetic background, have an aberrant regulation of hydrogen ion dynamics leading to a reversal of the intracellular to extracellular pH gradient (∆pHi to ∆pHe) in cancer cells and tissue as compared to normal tissue. This perturbation in pH dynamics rises very early in carcinogenesis and is one of the most common patho-physiological hallmarks of tumors. Recently, there has been a very large increase in our knowledge of the importance and roles of pHi and pHe in developing and driving a series of tumor hallmarks. This reversed proton gradient is driven by a series of proton export mechanisms that underlie the initiation and progression of the neoplastic process. In this context, one of the primary and best studied regulators of both pHi and pHe in tumors is the Na+/H+ exchanger isoform 1 (NHE1). The NHE1 is an integral membrane transport protein involved in regulating pH and in tumor cells is a major contributor to the production and maintainance of their reversed proton gradient. It is activated during oncogene-dependent transformation resulting in cytosolic alkalinization which the drives subsequent hallmark behaviors including growth factor- and substrate-independent growth, and glycolytic metabolism. It is further activated by various growth factors, hormone, the metabolic microenvironment (low serum, acidic pHe and hypoxia) or by ECM receptor activation. This review will present the recent progress in understanding the role the NHE1 in determining tumor progression and invadopodia-guided invasion/metastasis and recent patents for NHE1 inhibitors and novel therapeutic protocols for anti-NHE1 pharmacological approaches. These may represent a real possibility to open up new avenues for wide-spread and efficient treatments against cancer
Genetic Signature of Human Pancreatic Cancer and Personalized Targeting
No full textPancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11–12%.
Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is
slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis
Get PDFRecent research has highlighted the fundamental role of the tumour's extracellular metabolic microenvironment in malignant invasion. This microenvironment is acidified primarily by the tumour-cell Na+/H+ exchanger NHE1 and the H+/lactate cotransporter, which are activated in cancer cells. NHE1 also regulates formation of invadopodia - cell structures that mediate tumour cell migration and invasion. How do these alterations of the metabolic microenvironment and cell invasiveness contribute to tumour formation and progression
Variations on the Author
Get PDF“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
Molecular pathways shared between host-parasitoid interaction in insect and other animals: The case of teratocyte extracellular enolase
No full textMolecular pathways shared between host-parasitoid interaction in insect and other animals: The case of teratocyte extracellular enolase Introduction: Enolase is an ubiquitous metalloenzyme involved in the glycolytic pathway. Interestingly it appears also as a multifunctional protein. Enolases anchored on the outer surface of the plasma membrane are involved in tissue invasion mechanisms by the activation of Plasminogen.
Methods: To determine the Enolase localization and its capacity to bind and activate the plasminogen, experiments of immunogold labeling, indirect immunofluorescence staining, co-localization, binding and activation in vitro assay, Duolink in situ Proximity Ligation Assay (PLA) and dot blotting assay were carried out. Furthermore the Enolase ability to degrade extracellular matrix was in vitro evaluated by a Matrix digestion assay.
Results/Conclusion: We have identified an extracellular Enolase (Ae-ENO) produced by teratocytes, embryonic cells of the insect parasitoid Aphidius ervi (Hymenoptera, Braconidae). For the first time we demonstrate that Ae-ENO, although lacking a signal peptide, accumulates in cytoplasmic vesicles oriented towards the cell membrane. Ae-ENO binds and activates a plasminogen-like molecule inducing digestion of the host tissue and thereby ensuring successful parasitism. The results support the hypothesis of the existence of plasminogen-like proteins in invertebrates and their activation through mechanisms involving the surface enolase/fibrinolytic system that until now seemed to be exclusively found in vertebrates, and that is conserved across species. These findings also suggest that Ae-ENO is a novel and unique example of gene sharing in insects
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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