1,721,019 research outputs found
Role of Fibroblast Growth Factor Receptor 2 in Pancreatic Cancer: Potential Target for New Therapeutic Approach?
Full text linkFibroblast growth factors and their receptors play a key role in cell proliferation, migration and differentiation.
Fibroblast growth factor receptor 2 (FGFR2) is involved in carcinogenesis and its altered expression has been
shown in several tumors, such as breast, thyroid and pancreatic cancer. The two isoforms of FGFR2 gene, FGFR2-
IIIb (also known as KGFR) and FGFR2-IIIc have been shown to exert differential roles in pancreatic cancer. FGFR2-
IIIc supports pancreatic cell proliferation, while overexpression of FGFR2-IIIb is correlated to major invasion and
metastasis formation. This review focuses on the role of FGFR2 signaling in pancreatic adenocarcinoma and the
potential use of FGFR2 tissutal expression as a predictive and/or prognostic marker. Moreover, it will discuss about
the potential use of strategies for FGFR2 signaling inhibition in the treatment of pancreatic cancer
Use of KGF in the treatment of menopausal disorders
No full text1. I sintomi del climaterio possono essere anche molto severi. Le vampate di calore e la sudorazione, secondarie all'instabilità vasomotoria, interessano il 75% delle donne e possono protrarsi per un tempo variabile tra 1 e 5 anni. I sintomi vasomotori delle vampate coincidono con l’aumento di secrezione di LH. I sintomi psicologici ed emotivi, inclusi l'affaticamento, l'irritabilità, l'insonnia, l'incapacità a concentrarsi, la depressione, la perdita di memoria, la cefalea, l'ansia e il nervosismo, possono essere correlati alla deprivazione degli estrogeni e allo stress dovuto al passare degli anni e al cambiamento dei ruoli. L'interruzione del sonno, dovuta alle vampate ricorrenti, contribuisce ad aumentare l'affaticamento e l'irritabilità. Si possono verificare vertigini intermittenti, parestesie, palpitazioni e tachicardia. Sono comuni anche la nausea, la stipsi, la diarrea, le artralgie, le mialgie, il senso di freddo alle mani e ai piedi e l'aumento del peso. L'importante riduzione nella produzione di estrogeni causa dei profondi cambiamenti a livello della parte inferiore dell'apparato genitale; p. es., la mucosa vaginale e la cute vulvare diventano più sottili, la normale flora batterica si modifica e le piccole labbra, il clitoride, l'utero e le ovaie diminuiscono di dimensioni. L'infiammazione della mucosa vaginale (vaginite atrofica) può conferire alla mucosa un aspetto a fragola e una pollachiuria con tenesmo urinario, secchezza vaginale e dispareunia. Le donne tendono a perdere il tono dei muscoli pelvici e a sviluppare un'incontinenza urinaria, cistiti e vaginiti. La riduzione della libido è un disturbo frequente.
2. La diagnosi con la diversa gravità delle manifestazioni porta a necessità di terapie individualizzate, stabilendo il numero di cicli terapeutici in funzione della efficacia della terapia e della latenza dell'effetto terapeutico. La sostanziale bassa prescrizione della terapia ormonale sistemica che si riflette perfino nella bassa prescrizione della terapia locale denuncia una diffusa paura degli effetti collaterali in confronto alle reali necessità. La disponibilità di terapie che utilizzino estrogeni contenute in compresse a lento rilascio risulta più gradita in quanto consente di evitare l'utilizzo di eccipienti sgraditi per la presenza di un costante "bagnato", che fuoriesce, e sono meglio tollerate le terapie che utilizzino dispositivi di applicazione sterile e monouso che non coinvolgano l'introduzione delle dita in vagina, evitando inoltre il rischio di sovradosaggi.
3. L’adozione di terapie con fitoestrogeni e composti della soia è molto ben accettata anche se i risultati sono spesso deludenti a fronte di terapie lunghe e costose. Sono di seguito riportate le terapie più utilizzate ed i relativi prezzi di mercato: Ganassini Fitormil crema vaginale E. 13,80, Longlife isoflavoni soia 30 cpr 14,99; Estropiù bustine 20 E. 15,90; Rottapharm Estromineral Serena 20 cpr E. 17,50; Aboca Menovamp Soy integratore 30 cpr E. 18,45; Ducray Anacaps Concentre Integratore 30 caps E. 20,90; Rilastil Ganassini Fitormil Omega 30 Capsule E. 24,90. Il trattamento proposto nell’invenzione brevettuale consentirebbe di ottenere risultati sovrapponibili alla terapia ormonale con estrogeni senza aumento del rischio di insorgenza del cancro della mammella, con costi contenuti valutabili a seconda del veicolo d’utilizzo nello sviluppo industriale ed evitando terapie lunghe o applicazioni ripetute
Tyrosine 769 of the keratinocyte growth factor receptor is required for receptor signaling but not endocytosis
No full textKeratinocyte growth factor receptor (KGFR) is a receptor tyrosine kinase expressed on epithelial cells which belongs to the family of fibroblast growth factor receptors (FGFRs). Following ligand binding. KGFR is rapidly autophosphorylated on specific tyrosine residues in the intracellular domain, recruits substrate proteins, and is rapidly internalized by clathrin-mediated endocytosis The role of different autophosphorylation sites in FGFRs, and in particular the role of the tyrosine 766 in FGFR1, first identified as PLCgamma binding site, has been extensively studied. We analyzed here the possible role of the tyrosine 769 in KGFR, corresponding to tyrosine 766 in FGFR1, in the regulation of KGFR signal transduction and MAPK activation as well as in the control of the endocytic process of KGFR. A mutant KGFR in which tyrosine 769 was substituted by phenylalanine was generated and transfected in NIH3T3 and HeLa cells. Our results indicate that tyrosine 769 is required for the binding to KGFR and tyrosine phosphor-phosphorylation of PLCgamma as well as for the full activation of MAPKs and for cell proliferation through the regulation of FRS2 tyrosine phosphorylation, suggesting that this residue represents a key regulator of KGFR signal transduction. Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR. (C) 2004 Elsevier Inc. All rights reserved
Immunomodulatory effect of adipose-derived stem cells: the cutting edge of clinical application
Full text linkAdipose-derived stem cells (ASCs) represent a promising tool for soft tissue engineering as well as for clinical treatment of inflammatory and autoimmune pathologies. The well-characterized multi-differentiation potential and self-renewal properties of ASCs are coupled with their immunomodulatory ability in providing therapeutic efficacy. Yet, their impact in immune or inflammatory disorders might rely both on cell contact-dependent mechanisms and paracrine effects, resulting in the release of various soluble factors that regulate immune cells functions. Despite the widespread use of ASCs in clinical trials addressing several pathologies, the pathophysiological mechanisms at the basis of their clinical use have been not yet fully investigated. In particular, a thorough analysis of ASC immunomodulatory potential is mandatory. Here we explore such molecular mechanisms involved in ASC immunomodulatory properties, emphasizing the relevance of the milieu composition. We review the potential clinical use of ASC secretome as a mediator for immunomodulation, with a focus on in vitro and in vivo environmental conditions affecting clinical outcome. We describe some potential strategies for optimization of ASCs immunomodulatory capacity in clinical settings, which act either on adult stem cells gene expression and local microenvironment. Finally, we discuss the limitations of both allogeneic and autologous ASC use, highlighting the issues to be fixed in order to significantly improve the efficacy of ASC-based cell therapy
Potential dual role of KGF/KGFR as a target option in novel therapeutic strategies for the treatment of cancers and mucosal damages
No full textIntroduction: Keratinocyte growth factor (KGF) and its receptor KGFR play a pivotal role in regulating cell proliferation, migration, differentiation and survival, in response to injury and tissue repair. Altered expression of this pathway in cancer opened the way to the development of targeted therapy to achieve KGFR inhibition. Nevertheless, KGF administration has been demonstrated to ameliorate oral mucositis resulting from chemoradiotherapy, besides protecting epithelial cells against radiation-induced damage. Areas covered: This review focuses on the potential therapeutic interest of KGF/KGFR in two different areas: selective inhibition of KGFR signaling for the treatment of cancers characterized by upregulation of this pathway and administration of KGF to protect epithelial cells from induced damage. The review presents an overview of therapeutic strategies in both directions. Expert opinion: KGF/KGFR signaling can contribute to enhancing the malignant potential of epithelial cells and to promoting tumorigenesis. On the other hand, the therapeutic use of KGF in cancer patients provides epithelial protection, reducing chemotherapy side effects. FGFRs have become attractive antitumor targets and various inhibitors have been used to contrast tumor cell growth. The identification of KGFR-specific molecules might represent a promising therapeutic strategy that could increase the window of available agents and treatment methods
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
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Modulation of the expression of the FGFR2-IIIb and FGFR2-IIIc molecules in dermatofibroma
No full text[No abstract available
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