1,721,218 research outputs found
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
CD109 modulates tumorigenicity, cancer aggressiveness and PD-L1-mediated CD8+ T cell function via regulation of EGFR and STAT3 signaling in cervical squamous cell carcinoma
No full textCervical cancer is a common genital tract cancer associated with cancer-related deaths among women worldwide. Depending on the carcinoma stage, treatment includes surgery, chemotherapy, radiotherapy and immunotherapy, or combinations thereof. The recent development of immune checkpoint inhibitors is a future direction in cancer immunotherapy, because blockade of immune checkpoints unleashes CD8+ T cell-dominant antitumor immunity. Although extensive screening and vaccination are beneficial in decreasing disease burden, the molecular mechanisms underlying carcinogenesis and aggressiveness are not fully understood.
CD109 is a cell surface glycoprotein frequently detected in various squamous cell carcinoma (SCCs, included cervical cancer) although its pathogenic role in SCCs remains unclear. In a previous study, we found higher CD109 expression in spheroid cells than in their attached counterparts, both of which were derived from primary cervical tumor tissues. Therefore, elucidating the functional role of CD109 in the regulation of tumorigenic and aggressive properties and immunotherapy might provide a potential target for a novel treatment strategy.
In this study, CD109 expression was examined by immunohistochemistry with cervical tissue microarrays, and CD109 upregulation was observed in the cell membranes of cervical SCCs. Accordingly, four cervical cancer cell lines C33A, C4-1, CaSki and SiHa were used to functionally characterize the role of CD109 in cervical cancer. First, CD109(-) and CD109(+) subpopulations were isolated by fluorescence-activated cell sorting from C4-1 and CaSki cells. Compared with the CD109(-) subpopulation, CD109(+) cells displayed enhanced migration, cell proliferation, sphere-forming and anchorage-independent cell growth ability. Cervical cancer cell lines with high CD109 expression were then chosen for functional studies with siRNA knockdown and CRISPR/Cas9 knockout. In contrast to CD109-expressing cells, cells with silenced CD109 expression reversed the in vitro and in vivo tumorigenic and aggressive properties in cervical SCCs.
Furthermore, the expression of EGFR and STAT3 phosphorylation has been determined in CD109-expressing cells and CD109-silenced cells. The mechanism of this potential signal regulation has been examined in CD109-expressing cells through treatment with anti-EGFR antibody and knockdown of STAT3. CD109 induced EGFR-mediated STAT3 phosphorylation is believed to be responsible for cell migration, proliferation and the maintenance of a cancer stem-like cell (CSC) phenotype.
Additionally, CD109 upregulated PD-L1 expression in cervical cancer. Using CD8+ T cell/cervical cancer cell co-culture system, the effects of CD109 on CD8+ T cell apoptosis and cytokine secretion were evaluated by flow cytometric analysis. Blockade of CD109 has been found to suppress the apoptotic rate in CD8+ T cells and to enhance IFN-γ secretion, whereas CD109-expressing cancer cells inhibited IFN-γ secretion from CD8+ T cell. Furthermore, CD109 is positively correlated with EGFR and PD-L1 expression in cervical SCCs. CD109 facilitated PD-L1 expression via modulation of EGFR expression.
In summary, abundant CD109(+) populations in cervical cancer cells potentially contribute to carcinogenesis and aggressiveness, whereas silencing of CD109 expression reverses those properties. CD109 mediates cervical tumorigenicity and aggressiveness through CD109/EGFR/STAT3 signaling. Moreover, CD109 affects PD-L1-mediated CD8+ T cell function via regulation of EGFR in cervical SCCs. These findings may provide insight into potential molecular targets for a combined CSC-related and immunotherapeutic strategy against cervical SCCs.published_or_final_versionObstetrics and GynaecologyDoctoralDoctor of Philosoph
Oestrogen receptor subtypes in ovarian cancer
No full textpublished_or_final_versionabstractObstetrics and GynaecologyMasterMaster of Philosoph
Functional roles and therapeutic implication of UAP1, PGM3 and SOAT1 in ovarian cancer and CD8+ T cell-mediated immune response
No full textOvarian cancer is one of the most lethal gynecological malignancies in the world and is characterized by late diagnosis, frequent metastasis, chemotherapy resistance, and a high recurrence rate. The omentum is the most common metastatic site of ovarian cancer.
Deregulated metabolism is a hallmark of cancer. Targeting aberrant metabolic pathways in tumor cells not only directly affects tumors but also modulates immune cells such as CD8+ T cells in the tumor microenvironment, thereby altering tumor progression and metastasis. The suppression of CD8+ T cell-mediated immune responses can be relieved by the blockade of programmed cell death protein ligand 1 (PD-L1) immune checkpoint.
The hexosamine biosynthetic pathway (HBP) is a glycolysis-related pathway that produces UDP-GlcNAc, which is crucial for protein glycosylation. Key enzymes in this pathway, such as Phosphoglucomutase 3 (PGM3) and UDP–N-acetylglucosamine pyrophosphorylase 1 (UAP1), are essential for this process. Although previous studies have shown that inhibiting PGM3 or UAP1 suppresses tumor progression in multiple cancers, their roles in ovarian cancer have not been fully explored.
In this study, we investigated functional roles and therapeutic implications of PGM3 and UAP1 in ovarian cancer. We found that UAP1 expression was increased in metastatic lesions. Silencing of UAP1 by siRNA/shRNA in ovarian cancer cells reduced cell migration, invasion, proliferation, and stemness through EGFR/AKT signaling and regulation of metastasis-related FGF1 and EGR1, stemness-related SOX2/OCT4 and cell cycle-related p27 expression as assessed by RNA-sequencing analysis and Western blotting, whereas CRISPRa activation of UAP1 showed opposite effects. UAP1 and related signaling and downstream targets were upregulated upon treatment with conditioned medium from omental tissues. Moreover, UAP1 depletion downregulated PD-L1 expression and augmented the cytotoxic function of T cells. By in vivo imaging, UAP1 knockdown resulted in reduced tumor growth and metastatic dissemination.
We found higher expression of PGM3 in ovarian cancers. Inhibition of PGM3 by siRNA/shRNA or its inhibitor FR054 blocked proliferation, metastasis and stemness of ovarian cancer cells, whereas overexpression showed opposite effects. Mechanically, RNA-Seq and Western blotting showed reduced EGFR/AKT/ERK1/2 signaling. PGM3 knockdown resulted in reduced tumor growth and metastatic dissemination in mice.
Besides HBP, we examined Sterol-O acyltransferase 1 (SOAT1), the key enzyme of cholesterol metabolism, in ovarian cancer. SOAT1 functions by converting cholesterol and acyl-CoA into cholesterol ester and CoA-SH. Our study determined the effect of SOAT1 manipulation and drug inhibition in ovarian cancer cells on CD8+ T cell-mediated immune response. Inhibiting SOAT1 by siRNA or its inhibitor avasimibe in ovarian cancer cells impaired CD8+ T cell cytotoxicity, likely due to the upregulation of tumor-derived IL-6 and IL-8.
In conclusion, UAP1 and PGM3 significantly promote ovarian tumor progression through the EGFR/AKT signaling pathway, in which UAP1 plays a particularly important role in omental metastasis Targeting UAP1 and PGM3 (such as FR054) may be a potential therapeutic approach for ovarian cancer. Targeting SOAT1 in ovarian cancer may adversely affect the cytotoxic function of CD8+ T cells, which is an important factor to consider when developing therapeutic strategies.published_or_final_versionObstetrics and GynaecologyDoctoralDoctor of Philosoph
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
Role of exosomal miR-141 in pro-metastatic tumor-stroma interactions in ovarian cancer
No full textMetastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood. Previously, we showed that hsa-miR-141-3p (miR-141) is generally elevated and enhances anoikis resistance via targeting the KLF12/Sp1/survivin signaling cascade, facilitating metastatic cancer progression in ovarian cancer. Here, we report that Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), thereby facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted Yes-associated protein (YAP1), a key effector of the Hippo pathway, promoting Tafazzin (TAZ), reducing nuclear YAP1/TAZ ratio and enhancing Tafazzin (TAZ)- and TEAD1-mediated transcriptional activation of the oncogenic factors GROα and EMMPRIN in stromal fibroblasts. Genetic inhibition of YAP1 induced a direct increase in transcription of GROα and EMMPRIN, in turn, forming an ideal pre-metastatic niche in tumor microenvironment (TME) under conditions of chronic inflammation favoring metastatic colonization and progression. Conversely, enforced expression of YAP1 markedly reduced the levels of GROα and EMMPRIN. Stromal-specific knockout (cKO) of Yap1 in a murine model shaped a GROα-enriched microenvironment and promoted tumor colonization in vivo, but this effect was reversed after Cxcr1/2 depletion in ovarian cancer cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers.published_or_final_versionObstetrics and GynaecologyDoctoralDoctor of Philosoph
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