1,721,132 research outputs found
Identificazione di prodotti di geni regolati da NF-kB coinvolti nella sopravvivenza delle cellule tumorali
Esistono numerose evidenze sperimentali che mostrano il ruolo svolto da NF-kB nell’infiammazione e nel cancro. La sua attivazione costitutiva e’ stata riscontrata in numerose neoplasie umane sia solide che ematologiche e il blocco della sua attivita’in diverse linee cellulari tumorali blocca il potenziale oncogenico delle cellule neoplastiche. Un aspetto interessante dei rapporti tra infiammazione e cancro e’ che esiste una profonda interazione funzionale tra cellule neoplastiche e cellule infiammatorie. Questa interazione sembra essere dovuta alla produzione di fattori solubili sia da parte delle cellule infiammatorie che delle cellule neoplastiche, in grado di favorire la creazione di un microambiente favorevole alla sopravvivenza delle cellule. Scopo del presente progetto e’ l’identificazione di fattori solubili, i cui geni sono sotto il controllo trascrizionale di NF-kB, secreti dalle cellule neoplastiche, in grado di fungere da fattori di sopravvivenza delle cellule neoplastiche sia direttamente mediante un meccanismo autocrino, sia mediante il reclutamento di cellule infiammatorie
The Neutrophil Gelatinase-associated lipocalin (NGAL), a NF-kB regulated gene, is a survival factor for thyroid neoplastic cells
NF-κB is constitutively activated in primary human thyroid tumors, particularly in those of anaplastic type. The inhibition of NF-κB activity in the human anaplastic thyroid carcinoma cell line, FRO, leads to an increased susceptibility to chemotherapeutic drug-induced apoptosis and to the blockage of their ability to form tumors in nude mice. To identify NF-κB target genes involved in thyroid cancer, we analyzed the secretome of conditioned media from parental and NF-κB-null FRO cells. Proteomic analysis revealed that the neutrophil gelatinase-associated lipocalin (NGAL), a protein involved in inflammatory and immune responses, is secreted by FRO cells whereas its expression is strongly reduced in the NF-κB-null FRO cells. NGAL is highly expressed in human thyroid carcinomas, and knocking down its expression blocks the ability of FRO cells to grow in soft agar and form tumors in nude mice. These effects are reverted by the addition of! either recombinant NGAL or FRO conditioned medium. In addition, we show that the prosurvival activity of NGAL is mediated by its ability to bind and transport iron inside the cells. Our data suggest that NF-κB contributes to thyroid tumor cell survival by controlling iron uptake via NGAL
ROLE OF NF-kappaB IN THYROID CANCER.
Thyroid cancer is the most common neoplasia of the endocrine system and accounts for approximately 1% of all newly diagnosed cancer cases. Its incidence has rapidly grown over the past few decades. Although most thyroid carcinomas are of the well-differentiated papillary histology, and respond well to treatment with surgical resection followed by radioactive iodine ablation, tumors with more aggressive phenotype, such as follicular, poorly differentiated, anaplastic, and medullary cancers, lead to almost 1,500 patient deaths annually. Therefore, understanding molecular mechanisms that regulate the biology of these carcinomas could be helpful to identify new molecules acting as novel targets for therapeutic intervention. NF-kappaB has been recently shown to play an important role in thyroid cancer for its ability to control the proliferative and the anti-apoptotic signaling pathways of thyroid neoplastic cells. Oncogenic proteins RET/PTC, RAS and BRAF, that are involved in many aspects of thyroid carcinogenesis, can induce NF-kappaB activation in papillary, follicular, and medullary thyroid carcinomas, while constitutive de-regulated NF-kappaB activity has been found in anaplastic thyroid carcinomas. A number of NF-kappaB inhibitors have been demonstrated to induce anti-proliferative effects and/or massive apoptosis, especially in combination with radio- or chemo-therapy. The results obtained suggest that targeting NF-kappaB could be a promising strategy for advanced thyroid cancer treatment
Senescence and NFκB: A trojan horse in tumors?
The induction of senescence in tumor cells impairs transformation and promotes an anticancer immune response resulting from the production by senescent cells of cytokines and chemokines, an aspect known as “senescence-associated secretory phenotype” (SASP). Here we discuss recent findings regarding the role of NFκB in the modulation of the SASP and the consequent anticancer immune response
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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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