1,720,966 research outputs found
New Targeted Molecules for the Therapy of Ovarian Cancer
No full textPatients with high-grade serous ovarian cancer (HGSOC), the most aggressive epithelial ovarian cancer (EOC) subtype, have a 5-year survival rate of about 93% when diagnosed at an early stage, but it drops to 30-40% when diagnosed in the advanced stage. HGSOC aggressiveness is mainly caused by the late diagnosis (51% stage III, 29% stage IV) when the tumor has already spread in the peritoneal cavity. PIN1 is a unique peptidyl-prolyl isomerase that targets the phosphorylated Ser/Thr(Pro) motifs to regulate several key proteins in different signaling pathways. Pin1 is overexpressed in several cancer types and it regulates more than 40 oncogenes and 20 tumor suppressors. Many functions are modulated through PIN1-mediated isomerization such as cell cycle progression, cellular proliferation, invasion, migration, and apoptosis. Downregulation of Pin1 decreases tumor progression. Recently, Pin1 was shown to be overexpressed in ovarian cancer (OC) which, together with the high number of interactions with other proteins, makes Pin1 a promising target for HGSOC. The aim of this work is to investigate the effects of the PIN1 inhibitor VS10 on cancer cell lines and to find the molecular signaling pathways in which Pin1 is involved. Migration, mesothelial clearance assay, and the effects on spheroid formation and preformed spheroids were studied to better understand the effects on the metastatic process. Furthermore, in order to clarify the molecular mechanism that triggers the cytotoxicity induced by Pin1 inhibition in several OC cell lines, silencing Pin1 has been demonstrated to be associated with Ser473pAkt dephosphorylation by Western Blot (WB) analysis. Additionally, cell viability and colony-forming assays showed that Akt overexpression rescued the lethal phenotype due to Pin1 knockdown in OVCAR3 and KURAMOCHI OC cell lines. Among PIN1 inhibitors, All-trans retinoic acid (ATRA), a drug in clinic for the treatment of acute promyelocytic leukemia, has been demonstrated to be active on PIN1. Our group developed many PIN1 inhibitors including VS10, a non-covalent and selective molecule, which is active in killing cancer cells. ATRA and VS10 have been combined with first- and second-line chemotherapy drugs to treat SKOV3 cell line whether these drug combinations could work synergistically to improve current therapy. This drug combination screening showed that Doxorubicin and Caelyx act in synergy with both VS10 and ATRA. This drug combination was studied in 5 sensible and 2 OC cell lines resistant to cisplatin treatment. These results candidate Pin1 as a promising new molecular target for HGSOC patients' therapy.Patients with high-grade serous ovarian cancer (HGSOC), the most aggressive epithelial ovarian cancer (EOC) subtype, have a 5-year survival rate of about 93% when diagnosed at an early stage, but it drops to 30-40% when diagnosed in the advanced stage. HGSOC aggressiveness is mainly caused by the late diagnosis (51% stage III, 29% stage IV) when the tumor has already spread in the peritoneal cavity. PIN1 is a unique peptidyl-prolyl isomerase that targets the phosphorylated Ser/Thr(Pro) motifs to regulate several key proteins in different signaling pathways. Pin1 is overexpressed in several cancer types and it regulates more than 40 oncogenes and 20 tumor suppressors. Many functions are modulated through PIN1-mediated isomerization such as cell cycle progression, cellular proliferation, invasion, migration, and apoptosis. Downregulation of Pin1 decreases tumor progression. Recently, Pin1 was shown to be overexpressed in ovarian cancer (OC) which, together with the high number of interactions with other proteins, makes Pin1 a promising target for HGSOC. The aim of this work is to investigate the effects of the PIN1 inhibitor VS10 on cancer cell lines and to find the molecular signaling pathways in which Pin1 is involved. Migration, mesothelial clearance assay, and the effects on spheroid formation and preformed spheroids were studied to better understand the effects on the metastatic process. Furthermore, in order to clarify the molecular mechanism that triggers the cytotoxicity induced by Pin1 inhibition in several OC cell lines, silencing Pin1 has been demonstrated to be associated with Ser473pAkt dephosphorylation by Western Blot (WB) analysis. Additionally, cell viability and colony-forming assays showed that Akt overexpression rescued the lethal phenotype due to Pin1 knockdown in OVCAR3 and KURAMOCHI OC cell lines. Among PIN1 inhibitors, All-trans retinoic acid (ATRA), a drug in clinic for the treatment of acute promyelocytic leukemia, has been demonstrated to be active on PIN1. Our group developed many PIN1 inhibitors including VS10, a non-covalent and selective molecule, which is active in killing cancer cells. ATRA and VS10 have been combined with first- and second-line chemotherapy drugs to treat SKOV3 cell line whether these drug combinations could work synergistically to improve current therapy. This drug combination screening showed that Doxorubicin and Caelyx act in synergy with both VS10 and ATRA. This drug combination was studied in 5 sensible and 2 OC cell lines resistant to cisplatin treatment. These results candidate Pin1 as a promising new molecular target for HGSOC patients' therapy
Synthesis and Anticancer Activity of Palladium‐Butadienyl Complexes Bearing Picolyl‐NHC and Phosphine Ligands
No full textThis work presents the synthesis and full characterization of Pd(II)-butadienyl complexes incorporating picolyl-NHC or phosphine ligands (PPh3 or PTA). These complexes were evaluated against four different cancer cell lines and human lung fibroblasts. Our findings indicate a slightly lower antiproliferative activity of picolyl-NHC Pd(II)-butadienyl complexes compared to recently published ones featuring N−N, P−P, and C−C ligands but, above all, they exhibited selectivity for ovarian cancer cells. Additionally, trans-[PdX (phosphine)2C4(COOMe)4Y)] derivatives (X=Br, Cl and Y=CH3, Br) proved excellent anticancer activity across all tested cancer cell lines, especially the bisPTA complexes. Importantly, the IC50 values suggest minimal impact from the halide coordinated to palladium or that present in the butadienyl terminal position. Furthermore, the low activity observed towards non-cancerous cells underscores the potential of these synthesized Pd(II)-butadienyl compounds as promising candidates for further investigation in anticancer research
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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