1,721,025 research outputs found
Exploring novel personalized treatment options focusing on cancer stem cells
Get PDFIt is well known that cancer stem cells (CSCs) play a pivotal role in tumor metastasis, recurrence, heterogeneity, and resistance to chemotherapy and radiotherapy with poor prognosis in various cancers. Therefore, CSCs are promising targets for cancer treatment, which when effectively executed could ultimately improve patient prognosis. The work described in this thesis examined roles of some CSCs-related pathways including MTA3, ChRNA7, A-PaschiRNA, and mTOR in both cancer development, and maintenance and acquirement of cancer stemness, as defined by tumor cell dissemination and metastatic potential, as well as stem cell properties in cancer models. This thesis also revealed several underlying regulatory mechanisms of these pathways. Targeting these CSCs-related pathways using drugs that are currently existing or that will be developed could serve as a method to eliminate CSCs. Moreover, we also explored the potential of CSCs to predict patient response using CSCs-originating 3D cultured patient-derived organoids (PDOs), because accumulating evidence has showed CSCs can result in resistance to treatment. The preliminary results of this part suggest a potential of esophageal adenocarcinoma (EAC) patient’s tumor specific-derived organoids (ec-PDOs) to predict patient-specific responses to neoadjuvant chemoradiotherapy. Further characterization and optimization of ec-PDOs culture systems may offer huge potential as a model for predicting patient-specific responses to clinical neoadjuvant chemoradiotherapy for EAC patients. In conclusion, this thesis focused on CSCs to explore novel personalized treatment options
The use of organoids in the study of radiation response and therapeutic window
Get PDFThe efficacy of radiotherapy cancer treatment is hindered by tumor radioresistance and normal tissue side effects. In this thesis, in vitro stem cell-derived organoid models were developed and used to assess the contribution of both cancer and normal tissue stem cells in the radiation response, to study potential ways to optimize radiotherapy. The 3D nature of organoids may offer a radiation response model that better reflects the patient-specific in vivo response than traditional in vitro 2D cell line models. Many factors contribute to tumor radioresistance, however cancer stem cells related treatment resistance may play an important role. Using esophageal cancer organoids, the potential of altering the cancer stem cell population on reducing tumor radioresistance was assessed. Normal tissue side effects arise from unavoidable co-irradiation of normal tissue. Importantly the homeostasis of the normal tissue may be restored by surviving tissue stem cells. Reducing the dose to normal tissue is currently used in an attempt to reduce normal tissue side effects. However, the effects of a reduced dose to the normal tissue stem cells is not known. In this thesis, organoids are used to study the effects of different types of irradiation on normal tissue stem cells, while the effect of relatively low doses of irradiation on normal tissue was also investigated. It was shown that relatively low doses of irradiation have a disproportionately large impact on tissue function. Together, the work in this thesis contributes to the understanding of mechanisms which contribute to radioresistance and to radiation-induced side effects
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
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
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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
Investigating the Potential of Thyroid Gland Organoids to Restore Surgery-induced Hypothyroidism
Get PDFPatients who suffer from differentiated thyroid cancer are treated by surgical resection followed by radioactive iodine therapy to destroy potentially remaining malignant cells. As a result, these patients require lifelong daily suppletion with thyroid hormone medication to maintain normal blood levels. However, a large proportion of these patients experiences persistent side effects such as fatigue, constipation and weight gain. Therefore, they could benefit from an alternative form of treatment using autologous thyroid stem cells which would allow the regeneration of a functional thyroid gland. This could then restore the hormonal balance thereby improving their quality of life following cancer treatment.To achieve this goal, patient-derived thyroid cells are used to produce so-called organoids. These thyroid organoids exhibit physiological and genetic properties similar to the real organ, such as hormone production.In order to establish a clinical application of these thyroid organoids, experiments have been performed to investigate how the growth of the thyroid cells can be improved and stimulated for the purpose of transplantation. To this end, tracing experiments have been performed to identify a potential thyroid stem cell population. These experiments indicated that as thyrocytes age, they start to display plasticity which facilitates growth. Next, the optimal transplantation site for the organoids was investigated, which showed that implantation in the abdominal fat or axillary fat result in the most hormone production and are also the most accessible options. In summary, this dissertation combines fundamental, translational and pre-clinical studies to investigate the functionality and regenerative capacity of thyroid organoids
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