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Quang, Ly. "Photosensitizing effects of M-Tetrahydroxypheylchlorin on human tumor xenografts : correlation with sensitizer uptake, tumor doubling time and tumor histology /." [S.l.] : [s.n.], 1999. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Tulukcuoglu, Güneri Ezgi. "Development of microfluidic device for high content analysis of circulating tumor cells." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066583/document.
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Le cancer est l'une des principales causes de décès dans le monde. D'après la société américaine contre le cancer; en 2015, un quart des décès aux Etats-Unis est du au cancer du poumon avant même les maladies cardiaques. Cette situation nous incite et bien d'autres scientifiques dans le monde à développer des moyens plus efficaces de traitement, le diagnostic et le dépistage de la maladie. Parce que près de 90% des décès par cancer sont dus à des métastases, de nombreuses études se sont concentrées sur le mécanisme de métastases et sur son impact clinique. Les cellules tumorales circulantes (CTC) sont les cellules s’échappent de tumeurs primaires ou métastatiques pour rejoindre le flux sanguin périphérique, ces cellules sont un élément de transition dans le processus métastatique et portent ainsi des informations cruciales sur ce mécanisme encore mal compris. Les CTCs ont déjà montré leur potentiel comme biomarqueur de pronostic de la progression de la maladie et de l'indicateur de l'efficacité du traitement en fonction l’augmentation ou de la diminution de leur nombre. Leur caractérisation moléculaire peut également donner des informations vis à vis de cibles thérapeutiques possibles et des mécanismes de progression de la maladie ou de la résistance aux médicaments. Leur comptage au cours du traitement combiné avec leur caractérisation moléculaire devrait améliorer la prise en charge des patients dans le cadre de la médecine personnalisée. Cependant CTCs sont extrêmement rares, 1 à 10 cellules / ml de sang parmi les 106 globules blancs et 109 globules rouges, leur capture à partir du sang reste donc un challenge analytique. Dans les dernières décennies, Une grande variété de techniques d'enrichissement et de capture a été mise au point et l'approche microfluidique est l'une des méthodes efficaces, flexibles et à haut débit. Au sein de notre équipe, un dispositif microfluidique (système Ephesia) puissant pour la capture et l'analyse des cellules tumorales circulantes a déjà été mis au point précédemment. Le principe de capture est basé sur l'auto-assemblage de billes magnétiques greffées par des anticorps, grâce aux quelles les cellules sont enrichies via l’interaction Ab- l'antigène de surface EpCAM que l'on trouve communément dans les cellules cancéreuses d'origine épithéliale. Ce système a déjà été validé avec des lignées cellulaires et des échantillons de patients. Cependant, le système n'a pas permis l'isolement / détection des sous-populations de CTCs ou d'effectuer une caractérisation moléculaire très poussée. Par conséquent, mon projet de thèse vise à améliorer encore les capacités du système sur les deux principaux aspects: le ciblage sous-populations de CTC et à l'étude des interactions des protéines à la surface des CTCs dans le Système EphesiaMetastasis is the advanced stage of cancer progression and is the cause of 90% of deaths in cancer disease. During metastatic cascade, it is suggested that the successful metastatic initiation depends on the survival of circulating tumor cells (CTCs). CTCs are the cells that shed from the primary or secondary tumor sites into the blood circulation. it is now widely recognized as potential biomarker for companion diagnostics in which high number of CTCs in blood can indicate association with poor survival or high risk of disease progression. Besides, following the number of CTCs during the course of treatment can help to adapt the selected therapy and predict the treatment efficacy. On the other hand molecular characterization can provide patient stratification and identifying the therapeutic targets. However they are extremely rare in the bloodstream, estimated between 1-10 CTC among 6×106 leukocytes, 2×108 platelets and 4×109 erythrocytes per one mL of blood which makes their isolation very challenging. A very attractive way of isolation of CTCs is to integrate microfluidics. Microfluidics offers great advantages such as low volume of reagent consumption and short analysis times with automation as well as isolation and detection analysis can be integrated resulting in highly efficient biomedical devices for diagnostics. As parallel to state of the art, a powerful microfluidic device for circulating tumor cells capture and analysis had already been developed previously in our laboratory. The principle of capture is based on self-assembly of antibody-coated (EpCAM) magnetic beads in which the cells are enriched by EpCAM surface antigen which is found commonly in epithelial origin cancer cells. This system was already validated with cell lines and patients samples. However, the system did not allow isolation/detection of subpopulations of CTCs or performing high content molecular characterization. Therefore, my PhD project aimed at further improving the capabilities of the system on the main two aspects: targeting subpopulations of CTC and studying of protein interactions of CTCs in Ephesia System
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Romagnoli, Dario. "Identification and development of epigenetic tumor biomarkers through computational biology approaches." Doctoral thesis, Università di Siena, 2023. https://hdl.handle.net/11365/1227695.
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DNA-methylation alterations are common in cancer and display unique characteristics that make them ideal markers for tumor quantification and classification. In this study, we discuss the development and testing of a computational framework exploiting minimal DNA-methylation signatures composed by a few dozen informative DNA-methylation sites to quantify and classify tumor signals in tissue and cell-free DNA samples. Extensive analyses of multiple independent and heterogenous datasets including >7,200 samples demonstrate the capability of the framework to provide precise estimations of tumor content and to enable accurate classification of tumor type and molecular subtype. To evaluate its applicability in the clinical context, we designed an informed assay incorporating the minimal signatures for breast cancer. Using both artificial samples and clinical serial cell-free DNA samples from patients with metastatic breast cancer, we show that our approach provides accurate estimations of tumor content, sensitive detection of tumor signal and the ability to capture clinically relevant molecular subtype in patients’ circulation. This study provides evidence that an extremely parsimonious approach can be used to develop cost-effective and highly-scalable DNA-methylation assays that could support and facilitate the implementation of precision oncology in clinical practice.
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Herrera-Calderon, Oscar, Jorge Arroyo-Acevedo, Juan Rojas-Armas, Victor Chumpitaz-Cerrate, Linder Figueroa-Salvador, Edwin Enciso-Roca, and Johnny Tinco-Jayo. "Phytochemical Screening, Total Phenolic Content, Antioxidant and Cytotoxic Activity of Chromolaena laevigata on Human Tumor Cell Lines." SCIENCEDOMAIN international, 2017. http://hdl.handle.net/10757/622501.
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Aims: Cancer is the first cause of death in the Peruvian population; searching alternative treatments of medicinal plants constitute a promissory field to find new anticancer drugs. The main objective in this study was to evaluate the phytochemical screening, total phenolic content, antioxidant and cytotoxic activity of ethanol extract of Chromolaena laevigata (C. laevigata) on human tumor cell lines. Study Design: The fresh leaves of C. laevigata were soaked with ethanol followed by phytochemical screening using standard methods. Place and Duration of Study: Laboratory of Applied Chemistry, Faculty of Pharmacy and Biochemistry, Universidad Nacional San Luis Gonzaga de Ica, Ica, Peru; Laboratory “Abraham Vaisberg Wolach”, Universidad Peruana Cayetano Heredia, Lima, Peru. Methodology: Phytochemical screening was assessed by using chemical reactives. Total phenolic content (TPC) was developed using Folin Ciocalteu reactive and the antioxidant activity was determined against DPPH and ABTS radicals by spectrophotometry. The cytotoxic activity was determined on human tumor cell lines followed as: MCF-7, H-460, HT-29, M-14, K-562 and DU-145. Results: Phytochemical study confirmed flavonoids and phenolic compounds in ethanol extract. TPC resulted 45.21 ± 3.5 mg of gallic acid equivalent/g of dried extract. The highest antioxidant extract for DPPH and ABTS radical scavenging tests were IC50 = 11.66 ± 1.0 μg/mL, IC50= 12.45 ± 0.50 μg/mL respectively. Ethanolic extracts (μg/mL) showed a low cytotoxicity on human tumor cell lines (CI50 > 20 μg/mL) for DU-145, HT-29, MCF-7 and M-14. Whereas, for H-460, and K562 tumor cell lines showed high cytotoxicity. Conclusion: In our findings, C. laevigata demonstrated a high antioxidant and total phenolic content. The ethanol extract exhibited better cytotoxic effect compared with 5-FU. Hence, This medicinal plant could be effective to prevent chronical diseases as cancer and oxidative stress disorders.
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Furrer, Markus Kurt. "Isolated cytostatic lung perfusion : experimental assessment of different modalities and study of antitumor activity of human recombinant tumor necrosis factor-alpha /." [S.l : s.n.], 1998. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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König, Adrian. "Tumor necrosis factor alpha and interleukin 1 stimulate bone resorption in vivo as measured by urinary ³H-tetracycline extretion from prelabeled mice /." [S.l : s.n.], 1988. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Teng, Teng. "Loss of tumor suppressor RPL5/RPL11 does not induce cell-cycle arrest, but impedes proliferation due to reduced ribosome content and translation capacity: Implications in Diamond Blackfan Anemia." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1383645029.
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Leruste, Amaury. "Immune context of malignant rhabdoid tumors : description and identification of new therapeutic targets." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS050.
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Les tumeurs rhabdoïdes (TR) constituent un rare cancer indifférencié du jeune enfant et du nourrisson, avec un âge médian au diagnostic de 20 mois. Ces tumeurs sont caractérisées par une inactivation biallélique du gène suppresseur de tumeur SMARCB1, un des membres du complexe SWI/SNF, acteur majeur du remodelage de la chromatine, sans autre altération génomique récurrente. Le pronostic des TR est péjoratif, le taux de survie globale atteignant 30% dans la plupart des séries, malgré des approches thérapeutiques conventionnelles particulièrement agressives. Les approches d’immunothérapies ont obtenu un succès certain dans certains cancers de l’adulte, et récentes analyses de l’infiltrat immun des cancers pédiatriques ne montrent pas un fort taux de tumeurs infiltrées à l’exception de rare types de cancers dont les TR intracrâniennes. Nous avons donc procédé à une analyse multimodale de l’infiltrat immun de cohortes de patients ainsi que d’un modèle de TR murines établi dans notre laboratoire. Nous avons identifié une forte proportion de tumeurs infiltrées dans certains sous-groupes de TR. Cet infiltrat était composé à la fois de cellules myéloïdes incluant des populations au phénotype immunosuppresseur, et lymphocytaires T notamment de phénotype résident mémoire caractérisées par une forte expansion clonale probablement spécifique d’un antigène tumoral. Nous avons identifié des cibles thérapeutiques communes aux tumeurs humaines et au modèle murin syngénique, et trouvé que cibler l’infiltrat lymphocytaire T ou myéloïde était susceptible d’induire une réponse tumorale complète avec induction d’une mémoire immunitaire, confirmant le caractère immunogénique des TR, et apportant de nouvelles stratégies thérapeutiques utiles en clinique. Enfin, nous avons identifié que les TR étaient le site d’une réexpression de rétrovirus endogènes, dépendante de celle de SMARCB1, avec activation des voies de l’interféron, apportant une base à une immunogénicité des TR issue du génome non codantRhabdoid tumors (RT) are highly undifferentiated cancers occurring in infancy and early childhood, with a median age at diagnosis about 20 months. These tumors are characterized by the biallelic inactivation of SMARCB1 tumor suppressor gene, core member of the SWI/SNF complex, one major chromatin remodeling actor, in an otherwise highly stable genome. The prognosis of RT is dismal with overall survival hardly reaching 30% in most series, despite particularly aggressive conventional treatment. Immunotherapy approaches has gained a striking success within some adult cancer types and recent analyses of immune cell content of pediatric cancers don’t reveal a high rate of infiltrated tumors, except in few tumor types such as intracranial rhabdoid tumors. Then, we conducted a comprehensive analysis of the immune context of both human RT cohorts and a mouse RT model, including at single cell level. We identified a high recurrence of infiltrated tumors, in a RT-subgroup related manner, composed of both myeloid cells including cells with immune suppressive phenotypes, and T cells with notably a tissue resident memory phenotype demonstrating a high clonal expansion highly suggestive of immunogenicity. We identified common targetable immune populations between human and mouse RTs, and found that targeting both T and myeloid infiltrating cells was able to induce complete anti-tumor response with induced memory, confirming the immunogenic properties of RTs, and identifying new therapeutic strategies of clinical relevance. We finally identified that RTs were the site of SMARCB1-dependent endogenous retroviruses reexpression, with subsequent activation of interferon signaling, likely triggering the immune response in the context of RT, and providing a basis of non-coding genome-driven immunogenicity for these tumors
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Hobbs, Bryan. "Improving Educational Content: A Web- based Intelligent Tutoring System with Support for Teacher Collaboration." Digital WPI, 2013. https://digitalcommons.wpi.edu/etd-theses/225.
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Collaboration among teachers in some shape or form is becoming increasing popular among the educational system. The goal of this thesis is to determine whether teachers find value in collaboratively working in a Web environment and if we can use collaboration to improve educational content. We took a Web-based intelligent tutoring system, called ASSISTments, and incorporated a collaboration feature allowing teachers from around the Web to work together to create content for their students. The previous ASSISTments model did not allow for any form of collaboration; teachers using ASSISTments were not able to modify each other's content. By creating the opportunity for teachers to work together, we hypothesized that the educational content within ASSISTments would improve. To help improve education content among ASSISTments, we also deemed it necessary to improve the tool that teachers used to create problems for their students. Using surveys and interviews, we obtained feedback from teachers supporting our changes of the ASSISTments system and validating our claims that they found value in collaboratively working in a Web-based environment.
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Akbar, Shazia. "Tumour localisation in histopathology images." Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/c282ab9c-5776-400f-8440-f5ac9cf2f4ba.
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Immunohistochemical (IHC) assessment in cancer research is important for understanding the distribution and localisation of biomarkers at the cellular level. However currently IHC analyses are predominantly performed manually, increasing workloads and introducing inter- and intra-observer variability. Automation shows great potential in clinical research to reduce pathologists' workloads and speed up cancer research in large clinical studies. Whilst recent advancements in digital pathology have enabled IHC measurements to be performed automatically, the acquisition of manual annotations of tumours in scanned digital slides is still a limiting factor. In this thesis, an automated solution to tumour localisation is explored with the aim of replacing manual annotations. As an exemplar, human breast tissue microarrays stained with estrogen receptor are considered. Methods for automated tumour localisation are described with a focus on capturing structural information in tissue by adopting superpixel properties in a rotation invariant manner, suitable for histopathology images. To incorporate essential contextual information, methods which utilise posterior tumour probabilities in an iterative manner are proposed. Results showed pixel-level agreements between automated and manual tumour segmentation masks (κ=0.811) approach inter-rater agreement between expert pathologists (κ=0.908). A large proportion of disagreements between automated and manual segmentations were shown to correlate to minor discrepancies, inconsequential for IHC assessment. IHC scores extracted from automated and manual tumour segmentation masks showed strong agreements (Allred: κˆ=0.911; Quickscore: κˆ=0.922), demonstrating the potential of automation in clinical practice across large clinical trials.
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Schmid, Urs Dieter. "Management of obstructive hydrocephalus secondary to posterior foss tumors /." [S.l : s.n.], 1986. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Britt, Deanna C. "Thoughts, feelings, and actions : a restrospective study of the coping efforts of pediatric cancer patients in the context of the home, institution, and community /." This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-07282008-134837/.
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Yu, Kenny. "Cancer stem cells and tumour associated macrophages in Glioblastoma Multiforme." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/cancer-stem-cells-and-tumour-associated-macrophages-in-glioblastoma-multiforme(4b35d26b-3962-41c1-b944-f779e165e9ed).html.
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Glioblastoma Multiforme (GBM) is a primary malignant brain cancer, affecting children and adults and has a very poor prognosis. Up to 30% of the tumour mass consists of host derived immune cells, and a better understanding of how these cells affect tumour behaviour is required. These cells, called ‘Tumour Associated Macrophages’ (TAM) have been shown to occur in peripheral solid organ cancers, where they can cause local immune suppression, increase invasiveness and aid tumour growth. In the brain however, TAMs can consist of centrally derived microglia and peripherally derived macrophages, and although these cells could be exerting different effects on the tumour, there is currently no reliable way of distinguishing between the two. Cancer Stem Cells (CSC) are a subpopulation of cells within the tumour mass with stem-like features, are capable of self-renewal, and can recapitulate a tumour in an immunocompromised mouse host. It is thought that these cells play a role in disease recurrence and hence represent a potential target for anti-GBM therapies. In the first project we investigate the interaction between Cancer Stem Cells and TAMs. We first describe a method of culturing CSCs and TAMs from a single human patient sample, followed by an investigation into the functional properties of these cell types. We found functional differences between established cell line pairings of U87-MG and CHME3 versus primary patient derived CSCs and TAM cell line pairings. Polarisation of microglia/TAMs with lipopolysaccharide caused significant decrease in proliferative capacity of the GBM cell lines. Next we used a Non-Myeloablative Conditioning System (NMCS) to selectively replace the peripheral bone marrow compartment of wild type animals with labelled bone marrow cells, without disturbing brain homeostasis. We demonstrate that peripheral cells home exclusively to the orthotopically implanted tumour, and that some of these cells are CD11b+ and Gr1+, suggestive of myeloid derived suppressor cells (MDSC). We evaluate current CD45 based gating strategies for distinguishing peripheral and central cells and show them to be inadequate. Finally we compared the chemosensitivity profiles of different patient derived CSC lines using high throughput content screening (HTCS), against currently approved chemotherapeutic drugs and rank these drugs in a response space, based on HTCS parameters including 2D and 3D culture with and without irradiation. Differential chemosensitivities were noted between different patient derived cell lines. Drugs not currently used in the treatment of GBM such as Actinomycin D and Mitoxantrone were also identified using HTCS, suggesting the potential utility of such an approach to personalised treatments in GBM.
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Hashimoto, Kyoichi. "Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior." Kyoto University, 2018. http://hdl.handle.net/2433/230974.
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Claiden-Yardley, Kirsten. "Tudor noble commemoration and identity : the Howard family in context, 1485-1572." Thesis, University of Oxford, 2014. https://ora.ox.ac.uk/objects/uuid:5487809d-9066-4709-ace0-16b5debe825d.
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This thesis examines the relationship between the commemorative strategies of English noblemen in the period 1485-1572 and their identity both as individuals and as a social group. In particular, it will look at the Howard dukes of Norfolk in the context of their peers. The five chapters each address a different aspect of noble identity. The first two chapters deal with the importance of kinship and of status. The importance of kinship is evident across commemorative strategies from burial locations to the heraldry displayed at funerals to the references to ancestry in elegies. Having achieved a particular status, noblemen were defensive of their rank and the dues accorded to it. Funerals were designed to reflect social status and the choice of burial location could also indicate a concern with status. However, there was not always a correlation between the scale of commemoration and status. The third chapter examines the role that service to the Crown played in noble identity. Late medieval ideals of military service and a chivalric culture survived well in to the sixteenth century and traditional commemorative forms remained popular, even amongst noblemen newly ennobled from the ranks of the Tudor administration. Chapter four addresses the importance of local power to the nobility of the period. Burial and commemoration acted as a visible reminder of the social order and were of benefit in maintaining local stability. Noblemen could also use their death as a means of demonstrating good lordship through charity and hospitality. The final chapter examines the importance of religion to a nobleman's identity during a century of turbulent religious change. Studying commemorative strategies allows us to trace noble responses to religious change, the constraints on their public show of belief, and the ways in which they could express individuality.
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Oliveira, André Felipe de. "Síntese e caracterização de nanoestruturas de sílica SBA -16 contendo gadolinio-159 como potencial sistema nanoparticulado para o tratamento do câncer." CNEN - Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, 2013. http://www.bdtd.cdtn.br//tde_busca/arquivo.php?codArquivo=298.
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O câncer é uma das principais causas de morte em todo o mundo, sendo as neoplasias malignas de pulmão, estômago, fígado, cólon e mama em maior número. E, recentemente, observa-se na literatura um grande número de trabalhos onde novos materiais, especialmente nanoparticulados, vêm sendo estudados como carreadores de drogas e radioisótopos aplicados ao tratamento do câncer. Como materiais mesoporosos à base de sílica, graças a sua enorme área superficial e biocompatibilidade, têm sido estudados intensivamente propiciando amplas aplicações em várias áreas, o emprego da sílica SBA-16 nanoestruturada podem vir a ser um específico carreador de radioisótopos acumulando-os nas células malignas. Com isso a proposta deste estudo é desenvolver estudos in vitro utilizando SBA-16 capaz de concentrar seletivamente nas células malignas quantidades terapêuticas do radioisótopo Gadolínio-159 conduzindo-as a morte. Neste trabalho foi realizada a síntese da sílica mesoporosa ordenada, SBA-16 e a incorporação do complexo Gd-DTPA-BMA, assim como a caracterização química e estrutural. As técnicas utilizadas para analisar a ocorrência da incorporação do complexo de gadolínio na matriz de sílica foram análise elementar, espectroscopia de emissão atômica (ICP-AES), análise elementar (CHN), espectroscopia na região do infravermelho (FTIR), adsorção de nitrogênio (BET), difração de raios-x a baixos ângulos (SAXS) e análise termogravimétrica (TG). Para análise da morfologia da sílica pura utilizou-se a microscopia eletrônica de varredura (MEV) e microscopia eletrônica de transmissão (MET). Por espectroscopia de correlação de fótons (PCS) foi possível obter a medida do tamanho médio das partículas, o índice de polidispersividade (PDI) da sílica SBA-16 e o potencial zeta por anemometria de laser Doppler (LDA). Os resultados de incorporação analisados por ICP-AES indicaram que o material SBA-16 obteve um alto índice de incorporação do gadolínio (93 %). A cinética de liberação, em fluído simulado corpóreo, apresentou estabilidade considerável e baixo teor de liberação (1 %). A sílica mesoporosa SBA-16 apresentou viabilidade celular em contato direto com cultura de células. As amostras, com gadolínio incorporado na matriz de sílica, após da irradiação não apresentaram atividade citotóxica expressiva, o que implica que esses estudos devem aprimorados para que mais pesquisas na área de nanobiotecnologia sejam realizadas.Cancer is a leading cause of death worldwide, and malignant neoplasms of the lung, stomach, liver, colon and breast in greater numbers. And recently observed in the literature a large number of reviews where new materials, especially nanoparticle, has been studied as drug carriers and radioisotopes applied to cancer treatment. How mesoporous materials based on silica, thanks to its huge surface area and biocompatibility, have been studied intensively providing broad applications in various areas, the use of nanostructured silica SBA-16 might be a carrier specific radioisotope accumulate in the cells malignant. Thus the aim of this study is to develop in vitro studies using SBA-16 can selectively concentrate in malignant cells therapeutic amounts of the radioisotope Gadolinium-159 escorting them to death. This work was performed orderly synthesis of mesoporous silica, SBA-16 and incorporating the complex Gd-DTPA-BMA, as well as chemical and structural characterization. The techniques used to analyze the occurrence of the incorporation of the gadolinium complex in the silica matrix were elemental analysis (CHN), atomic emission spectroscopy (ICP-AES), infrared spectroscopy (FTIR), nitrogen adsorption (BET), small-angle X-ray scattering (SAXS) and thermogravimetric analysis (TG). To analyze the morphology of pure silica used the scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By photon correlation spectroscopy (PCS) it was possible to obtain a measure of mean particle size, the polydispersity index (PDI) of the silica SBA-16, and the zeta potential by laser Doppler anemometry (LDA). The results of incorporation analyzed by ICP-AES indicated that the material SBA-16 had a higher rate of incorporation of gadolinium (93%). The release kinetics in simulated body fluid, showed considerable stability and low release (1%). The mesoporous silica SBA-16 showed cell viability in direct contact with cell culture. Samples with gadolinium incorporated in the silica matrix after irradiation showed no significant cytotoxic activity, implying that these studies should improved so that more research in nanobiotechnology are performed.
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Porto, Hellen Karine Paes. "Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas." Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tede/4437.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
It is well known that metal complexes have been used as therapeutic agents since ancient times. However, with the success of cisplatin development as an antitumor agent in 1960inorganic drugs come to mainstream again. Despite the success of platinum compounds, serious problems are encountered when administering these drugs, such as nephrotoxicity, neurotoxicity and acquired resistance. In face of these problems other chemotherapeutic agents, less toxic to the organism and more efficient, become necessary. Several studies have been shown that ruthenium compounds present high selectivity for tumor cells and low systemic toxicity when compared to platinum (II) compounds. The present study evaluate antimor activity of two new ruthenium(II) compounds associated with amino acids, alanine and tryptophan. Ruthenium(II) compound were tested against B16-F10 and Ehrlich tumor cell lines and L-929 basal line using MTT assay, at different concentrations (0.2 - 200 mM) for 48 hours of treatment. Cell cycle analysis and apoptosis induction analyses by flow citometry and comet assay for DNA damage were also performed The IC50 values were estimated as 16.17 mM (RuAla) and 7.75 mM (RuTrp). The compound RuAla proved to be specific for the B16-F10 tumor cell line and showed a significant ability to change cell cycling profiles, arresting cells inG0/G1 phase, and also inducing cell death by apoptosis within 48 hours of treatment. The compound RuTrp showed high cytotoxic potential against Ehrlich tumor, interfering cell cycle kinetics,causing cell cycle arrest in G0/G1 phase and inducing cell death by apoptosis. Comet assay presented damage to genetic material only when cells were trated with high concentrations of RuTrp. , RuAla and RuTrp presented relevant cytotoxic activities towards tumor lineages tested in vitro. Thus, more specific tests are needed to elucidate the mechanism of action of these promising The ruthenium(II) compounds.
Sabe-se que complexos metálicos têm sido usados como agentes terapêuticos desde a antiguidade. No entanto, o reaparecimento de drogas inorgânicas iniciou-se em 1960 com o desenvolvimento e o sucesso da cisplatina como agente antitumoral. Apesar do sucesso dos compostos de platina, sérios problemas são enfrentados durante a administração dessas drogas, como nefro e neurotoxicidade e resistência. Em vista dos problemas relacionados com o tratamento a base de platina, outros quimioterápicos que sejam menos tóxicos ao organismo e mais eficientes tornam-se necessários. O estudo da atividade antitumoral se destaca com os complexos de rutênio, os quais têm demonstrado alta seletividade para células tumorais e baixa toxicidade sistêmica, quando comparados aos compostos de platina (II). O presente estudo teve como objetivo avaliar dois novos compostos de Rutênio (II), associados a aminoácidos, Alanina e Triptofano, com potencial antitumoral. No ensaio de citotoxicidade, os dois complexos de Rutênio foram avaliados frente a duas linhagens tumorais (B16-F10, Tumor de Ehrlich) e uma linhagem basal (L-929) através do teste de MTT, em diferentes concentrações dos compostos (0,2 – 200 μM) por 48 horas de tratamento. Foram realizados também análises de ciclo celular, ensaio cometa e teste Anexina V para avaliação do mecanismo de morte. Análise estatística para comparação entre os grupos tratados e controle foi utilizado Anova segundo um único critério e pós-teste Dunnet’s (software GraphPad Prism V4). Os valores de IC50 estimados foram 16,17μM (RuAla) e 7,75μM (RuTrp). O composto RuAla mostrou-se específico para a linhagem B16-F10 e apresentou capacidade de alterar o ciclo celular das células, parando a ciclagem em fase G0/G1, e também demonstrou induzir morte celular por apoptose em 48 horas de tratamento. O composto RuTrp apresentou alto potencial citotóxico frente ao Tumor de Ehrlich, interferiu na cinética do ciclo celular, parando o ciclo celular em fase G0/G1. O RuTrp também induziu morte celular por apoptose, entretanto somente apresentou dano ao material genético em altas concentrações. Todavia, teste mais específicos são necessários para a elucidação do mecanismo de ação desses dois novos composto a base de Rutênio (II) com promissores resultados anti-câncer.
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Burgett, Monica E. "Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1466174564.
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Velinov, Nikolay. "Matrix metalloproteinase-19 is a predictive marker for tumour invasiveness in patients with oropharyngeal squamous-cell carcinoma /." Bern : [s.n.], 2007. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Neupane, Rachit. "BMI1 is a context-dependent tumor suppressor that is a barrier to dedifferentiation in non-small cell lung adenocarcinoma." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122061.
Full textAbstract:
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019
Cataloged from student-submitted PDF version of thesis. "May 2019."
Includes bibliographical references.
Predictive value is expected when preclinical models of disease are used for research. However, not all models appropriately mimic the disease progression or the treatment paradigm in the clinic. This thesis addresses an epigenetic regulator, Bmi1, which acts in stem cells to maintain their proliferative and self-renewal capacity primarily through silencing of the Ink4a/Arf locus. Bmi1 has been proposed as a good therapeutic candidate in cancer because of its presumed role in maintaining tumor propagating cells (TPCs). This conclusion is based on the observed tumor suppressive effects of Bmi1 deletion in in vitro cell culture models, in vivo transplant models, and autochthonous models in which Bmi1 was absent throughout development. However, to date, no one has assessed the consequences of deleting Bmi1 in existing autochthonous tumors, to mimic patient treatment in the clinic.
To accomplish this, we have generated a mouse model that allows induction of autochthonous lung adenocarcinoma, driven by oncogenic Kras and Tp53 loss (KP LUAD), and subsequent deletion of Bmi1 specifically within the tumor cells once more than half the tumors progress to grade 3 or higher. We confirmed that this model yielded Bmi1 loss that was tumor-specific and almost complete. We then aged tumor bearing mice for up to seven weeks post Bmi1 deletion to determine the impact on LUAD. Unexpectedly, Bmi1 deletion did not yield significant tumor suppression. Instead, gene expression analyses of Bmi1 deficient tumor cells revealed upregulation of a gastric gene expression program that is a known marker of lung tumor progression towards a more aggressive state in the KP LUAD model. Additionally, single cell sequencing showed that Bmi1 deficient tumors contained a higher frequency of cells that expressed previously described markers of TPCs and metastasis.
We also extended these findings to colorectal cancer where we show that deletion of Bmi1 is not tumor suppressive in either in vitro organoids or orthotopic transplants. Given these findings, we conclude that deletion, or inhibition, of BMI1 in existing tumors will be ineffective for cancer treatment in the contexts examined, and potentially deleterious because it can enable acquisition of alternate differentiation states that promote tumor progression.
by Rachit Neupane.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
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Allinson, David John. "The rhetoric of devotion : some neglected elements in the context of the early Tudor motet." Thesis, University of Exeter, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286476.
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Bucher, Katharina M. I. "The tumour suppressor gene p53 in the horse : identification, cloning and sequencing : its possible role in the pathogenesis of equine sarcoid /." [S.l.] : [s.n.], 1995. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Lima, Renato Sousa. "Biossensor condutométrico sem contato em microchip contendo ácido fólico como biorreceptor." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/75/75132/tde-27082010-104803/.
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Este trabalho descreve o desenvolvimento de um biossensor contendo transdução condutométrica sem contato (C4D, capacitively coupled contactless conductivity detection) e ácido fólico (FA) como biorreceptor em microchip, uma nova alternativa que poderá ser utilizada na determinação do biomarcador tumoral FR-α. Essa espécie exibe interações com FA altamente específicas, com constantes de formação da ordem de 109-1010. Os dispositivos microfluídicos, os quais consistiram de uma lâmina de vidro (integrando os eletrodos), dielétrico (contendo a fase biossensora) e substrato de poli(dimetilsiloxano) (PDMS, incorporando os microcanais), foram fabricados utilizando-se processos de fotolitografia e deposição de filmes finos em fase vapor. Objetivando melhorias nos níveis de detecção da C4D, estudos de sensibilidade com base em parâmetros da curva analítica foram conduzidos alterando-se a natureza do dielétrico e a configuração dos eletrodos. Posteriormente, estudos de caracterização foram realizados para as superfícies modificadas com os intermediários de imobilização; condições reacionais distintas (reagente, concentração, solvente e tempo) foram consideradas. As técnicas de microscopia eletrônica de varredura e espectroscopia de fotoelétrons excitados por raios-X foram usadas, respectivamente, a fim de se verificar a possível formação de aglomerados e permitir determinações qualitativas e quantitativas sobre as composições químicas das superfícies. Como resultado dos experimentos de sensibilidade e caracterização de superfície, adotamos os parâmetros seguintes para os ensaios de interações biomoleculares posteriores: filme de SiO2 como dielétrico, eletrodos seletivos à C4D com formato retangular e orientação antiparalela e monocamadas automontadas do reagente 3-aminopropil(trietoxisilano) como intermediário de imobilização de FA. As duas etapas finais do trabalho foram: otimização do tempo de funcionalização com FA (3, 5 e 7 h) e caracterização da fase biossensora, realizada a partir de medidas de C4D e microscopia de força atômica (AFM). Para o primeiro caso, os microchips foram aplicados a um padrão de anticorpo monoclonal específico a FA (α-FA). Os ensaios biomoleculares indicaram uma adsorção efetiva de FA junto à superfície de SiO2 silanizada, sem a ocorrência (ao menos em níveis significativos) de impedimentos estéricos de sua espécie bioativa. Dentre os tempos de funcionalização investigados, 3 h foi aquele que resultou em uma maior sensibilidade do método. Em termos da etapa de caracterização eletroquímica da fase biossensora, seus resultados mostraram haver correlação entre a resposta analítica e as interações FA/α-FA. Em adição, conforme indicaram as medidas de AFM, não houve alterações drásticas na morfologia do substrato (SiO2) em função dos processos de modificação química de superfície. Por fim, o uso da C4D como uma técnica de transdução em biossensores mostrou-se uma alternativa promissora para a análise do biomarcador tumoral FR-α. Dentre outros aspectos, essa plataforma analítica requer uma instrumentação simples, barata e portátil, não apresenta inconvenientes relacionados ao contato eletrodo/solução, dispensa o uso de mediadores redox e permite a determinação simultânea de multianalitos. Neste ínterim, alterações no transdutor devem ser implementadas visando um aumento na sensibilidade do método, o qual representa seu fator limitante principal.This work describes the development of a biosensor containing capacitively coupled contactless conductivity transduction (C4D) and folic acid (FA) as bioreceptor in microchip, a new alternative that can be used in FR-α tumor biomarker analysis. FR-α exhibits highly specific interactions with FA, showing formation constants of the order of 109-1010. The microfluidic devices consisted of a glass layer (integrating the electrodes), dielectric (containing the biosensor phase), and poly(dimetilsiloxane) substrate (PDMS, incorporating microchannel). The microfabrication stage evolved photolithography processes, metal adsorption via sputtering, and plasma-enhanced vapor film deposition. In order to improve detection levels of C4D, sensitivity studies were conducted by changing the dielectric nature and electrode configuration. Through flow analysis with given electrolyte standards, the limits of detection and quantification were calculated based on analytical curve parameters. Subsequently, researches were performed to characterize the modified surfaces with immobilization intermediate considering reaction conditions distinct (reagent, concentration, solvent, and time). The techniques of scanning electron microscopy and X-ray photoelectron spectroscopy were employed, respectively, aiming to verify the clusters formation and allow qualitative and quantitative determinations about the surfaces chemical composition. From the results of sensitivity experiments and surface characterization, we adopt the following parameters for the biomolecular interactions assays: SiO2 film as dielectric, C4D selective electrodes with rectangular shape and antiparallel orientation, and self-assembled monolayers of 3-aminopropyl(triethoxysilane) as intermediary for immobilization of FA. The two final steps of the work were: optimizing the FA functionalization time (3, 5, and 7 h) and phase biosensor characterization, made from measures of C4D and atomic force microscopy (AFM). For the first case, due to the absence of FR-α standard for purchase, the microchips were applied to FA specific monoclonal antibody (α-FA). The biomolecular assay indicated effective adsorption of FA, without occurrence (at least in significant levels) of steric hindrance of its bioactive specie. Among the investigated times of functionalization, 3 h resulted in a higher sensitivity of the method. In terms of biosensor phase electrochemical characterization stage, their results evidenced correlation between analytical response and FA/α-FA interactions. Additionally, as the AFM measurements showed, drastic changes in the morphology of the substrate (SiO2) with the surface modification processes did not occur. Finally, the use of the C4D as transduction technical in biosensors proved to be a promissory alternative for FR-α tumor biomarker analysis. Among other features, this platform has not drawbacks related to the electrode/solution contact, dispenses the use of redox mediators, allows the simultaneous determination of multianalytes, and employs an instrumentation that is simple, cheap, and portable. Nevertheless, changes in the transducer should be implemented to increase the method sensitivity, which represents its main limiting factor.
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Dumbuya, Alieu. "Optimization of Tutorial Contents, Tutorial Actions and Tutorial Strategies for Student-Tutor Interaction in e-Learning." INTELLIGENT MEDIA INTEGRATION NAGOYA UNIVERSITY / COE, 2005. http://hdl.handle.net/2237/10388.
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Britt, Deanna C. "Thoughts, feelings, and actions: a retrospective study of the coping efforts of pediatric cancer patients in the context of the home, institution, and community." Diss., Virginia Tech, 1992. http://hdl.handle.net/10919/38914.
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This study was a retrospective examination of the experiences of pediatric cancer patients and their families from a contextual perspective. The home, institution, and community contexts were investigated to reveal their influences on the coping efforts of the study participants. Ten families of children with cancer were interviewed, and data were analyzed qualitatively. Walker's (1985) family stress model and Lazarus' (1984) coping paradigm guided the study.
The findings indicated that children were ambivalent in their attitudes toward the disease process. While they did not enjoy painful procedures, sickness, frequent hospitalizations, and baldness, they did welcome the special attention brought about by these stressors. Many of the children in the study understood the impact of their illness on the family. They felt guilty about family financial pressures, parental marital problems, and sibling conflicts that resulted from their cancer. Most feared relapse and death but hid their feelings to protect their parents.
Mothers handled the stress of their child's illness by learning all they could about the disease, focusing completely on the sick child, and protecting the child from further harm. Fathers tended to take on the role of "strong one" while worrying about finances and attempting to keep the families together. Differing ways of coping between mothers and fathers often caused feelings of resentment and marital difficulties. Parental attitudes toward the staff at the medical center varied from trust, to wariness, to dependency. Parents enjoyed the support of family, friends, and community during the diagnosis phase, but felt bitter about the lack of support they received during the treatment and completion stages. Some parents believed that their exposure to the
stressors of the illness process led to personal growth that they would not have experienced otherwise. Many parents emerged from the cancer ordeal with a desire to help others who were battling childhood cancer. They became involved in a variety of community agencies that served the families of children with cancer.Ph. D.
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Ketteler, Julia [Verfasser], and Diana [Akademischer Betreuer] Klein. "Role of Caveolin-1 for modulating the radiation response in the context of tumor stroma interactions / Julia Ketteler ; Betreuer: Diana Klein." Duisburg, 2020. http://d-nb.info/1216038929/34.
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McCutchan, Grace. "Understanding the influences on cancer symptom presentation behaviour in the context of socioeconomic deprivation : development of a targeted cancer awareness intervention." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/96993/.
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Inequalities in cancer survival outcomes can partly be explained by prolonged cancer symptom presentation among socioeconomically deprived groups. This PhD aimed to (1) understand the barriers to cancer symptom presentation among low socioeconomic groups and (2) develop a targeted cancer awareness intervention to promote timely symptom presentation. The COM-B (Capability, Opportunity, Motivation-Behaviour) model was selected to guide understanding of the influences on cancer symptom presentation behaviour. Systematic review and qualitative methods (30 in-depth interviews and six focus groups) were employed to identify the factors influencing symptom presentation. Findings from these studies and a scoping review of cancer awareness interventions were used to inform intervention development, guided by the Behaviour Change Wheel. The intervention was tested for acceptability with two groups of potential users. The combination of poor cancer symptom knowledge, fearful and fatalistic beliefs about cancer, and barriers such as problems associated with obtaining and accessing a primary care appointment prolonged cancer symptom presentation among low socioeconomic groups. In addition, the wider social and environmental opportunities available to people from low socioeconomic groups including economic hardship and negative experiences of cancer were identified as key influences on behaviour. An intensive community group based educational session was developed targeted at current or former smokers and family members of smokers, aged 40 years or over from socioeconomically deprived communities. Content was developed to increase cancer symptom knowledge, modify beliefs and enable timely symptom presentation by utilising strong social networks in the community. Findings from user testing confirmed that group education was an acceptable mode of intervention delivery. Understanding the complex interaction between individual psychological characteristics and the wider environment in which people from low socioeconomic groups live in is essential for modifying cancer symptom presentation behaviour. Community education could be used as a strategy to engage low socioeconomic groups in early cancer detection and warrants further feasibility and pilot testing.
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Tra, John. "Effects of dietary linoleic and stearic acids on the PGE2 content of mammary tumors in strain a/s female mice." Virtual Press, 1998. http://liblink.bsu.edu/uhtbin/catkey/1115750.
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Prostaglandin E2 (PGE2), a byproduct of arachidonic acid metabolism, has been suspected to be involved in tumor promotion. It has been suggested that diet may modulate PGE2 level in organisms thus affecting the implantation and growth of the tumor tissue. PGE2 content was investigated in mice fed ad libitum four types of fatty acid diets: saturated fatty acid diets: a stearic acid and a palmitic acid, and polyunsaturated fatty acid diets: a low fat (safflower 1%) and a high fat diet (safflower 15%). Tumor cells were implanted subcutaneously in mice and harvested when tumors reached .05- 4g. The extracted PGE2 were derivatized and quantified by High Performance Liquid Chromatography (HPLC). The results showed that there is a negative correlation between the level of PGE2 and the size of the tumors. PGE2 level declined as the tumor grew. This suggests that during the early stage of growth the tumor requires higher level of PGE2 to boost its growth. As the tumor becomes more adapted to its environment, it no longer depends on PGE2 to survive. Diet was also seen to be important in tumor suppression. Saturated fatty acid diet (SA-1) showed a suppressive effect on tumor growth. A visual comparison showed that polyunsaturated high fat diet produced more PGE2 than saturated fatty acid. This high level of PGE2 correlate with the highest tumor weights obtained in the Polyunsaturated high fat diet group.Department of Biology
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Stather, David. "Prevalence of possible immune resistance mechanisms of acute leukemias within the context of vaccination strategies using the Wilms tumor gene-1 (WT1)." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16573.
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Die Studie auf die diese Arbeit aufbaut untersuchte die Immunogenität einer Wilms-Tumorgenprodukt-1-(WT1)-Peptid-Vakzinierung bei Patienten mit einer WT1-exprimierenden akuten myeloischen Leukämie (AML) ohne weitere Behandlungsoption. Trotz dem initalen immunologischen, molekularen und vorläufigen Nachweis einer möglichen klinischen Effektivität bei AML-Patienten, konnte nur in wenigen Fällen eine längerfristige Wirksamkeit dokumentiert werden. Es ist bekannt, dass eine Krebs-Immuntherapie durch Immunevasions-Mechanismen des Tumors beeinträchtigt werden kann. Da Analysen zu Mutationen oder Verlust des WT1-Epitops oder Epitop-flankierender Sequenzen keine Auffälligkeiten zeigten, konnte eine reduzierte Präsentation oder Erkennung des Epitops ausgeschlossen werden. Aus diesem Grunde sollte diese Arbeit weitere mögliche Immunevasions-Mechanismen identifizieren. Als Grundlage wurden Tumor-assoziierte Effekte, immunmodulatorische Faktoren und funktionelle Einschränkungen der Immunzellen in den Mittelpunkt der Untersuchungen gestellt. Die ermittelten Daten zeigen, dass in unserem spezifischen Therapieansatz, der wiederholten Vakzinierung von AML-Patienten mit einem HLA-A201-restringierten WT1126–134 -Epitop in Kombination mit GM-CSF und KLH, eine eingeschränkte T-Zell-Funktionalität einen wesentlichen Grund für die beobachtete verminderte Therapieeffizienz darstellt. Immunresistenzmechanismen leukämischer Blasten spielen hierbei keine übergeordnete Rolle, individuelle Effekte können aber nicht ausgeschlossen werden. Ebenso scheint es, dass auch die Präsenz von immunregulatorischen Zellen wie Tregs oder MDSCs nicht durch die Vakzinierung manipuliert wird und dass diese keinen generellen Einfluss auf die Therapieeffizienz ausüben.The foregoing study investigated the immunogenicity of Wilms’ tumor gene product 1 (WT1)-peptide vaccination in WT1-expressing acute myeloid leukemia (AML) patients without curative treatment option. Despite the first immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, only in a few cases long-lasting responses could be documented. It is known that enduring efficacy of cancer vaccines may be limited due to immune escape mechanisms. On this account, we chose to work on three front lines: Investigations of immune modulatory counter-attack-mechanisms of the tumor, functional deficiencies of the T cell compartment and the presence of immune regulatory cells. The generated data demonstrates that in our specific setting, in which AML patients received consecutive vaccinations with HLA-A201-restricted WT1126–134 epitope together with GM-CSF and KLH, impaired vaccine efficacy is mainly attributed to restricted T cell functionality. Immune resistance mechanism exerted by leukemic blasts do not generally influence clinical outcome in our setting, neither do inert immunoregulative mechanisms like Treg or MDSC, respectively.
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HOSHINO, MUNEMITSU, MUTSUSHI MATSUYAMA, OSAMU TAGUCHI, MORIAKI KUSAKABE, WORAWIDH WAJJWALKU, JIN LU, TOYOHARU YOKOI, et al. "Establishment and Characterization of Immortalized Non-Transplantable Mouse Mammary Cell Lines Cloned from a MMTV-induced Tumor Cell Line Cultured for A Long Duration." Nagoya University School of Medicine, 1991. http://hdl.handle.net/2237/17515.
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Schleifenbaum, Stefan, Michael Schmidt, Robert Möbius, Thomas Wolfskämpf, Christian Schröder, Ronny Grunert, Niels Hammer, and Torsten Prietzel. "Load and failure behavior of human muscle samples in the context of proximal femur replacement." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-204698.
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Background: To ensure adequate function after orthopedic tumor reconstruction, it is important to reattach the remaining soft tissue to the implant. This study aimed at obtaining mechanical properties of textile muscle-implant and muscle-bone connections in a preliminary test. Methods: Two groups of soft-tissue attachment were mechanically tested and compared: Native bone-muscle samples obtained from human femora and muscles attached to a prosthetic implant by means of Trevira® attachment tubes. Additionally, muscle samples were tested with muscle fibers aligned parallel and perpendicular to the tension load. A uniaxial load was exerted upon all samples. Results: Failure loads of 26.7 ± 8.8 N were observed for the native bone-muscle group and of 18.1 ± 9.9 N for the Trevira® group. Elongations of 94.8 ± 36.2 % were observed for the native bone-muscle group and 79.3 ± 51.8 % for the Trevira® group. The location of failure was mainly observed in the central area of the muscle fibers. Muscle fibers with parallel fiber orientation (47.6 ± 11.5 N) yielded higher tensile strength than those with perpendicular fiber orientation (14.8 ± 4.1 N). Conclusions: Our experiments showed that higher forces were transmitted in the origin and insertion areas than in areas of flat soft tissue reconstruction using attachment tubes. The data indicate that the tested material allows reattaching muscles, but without reinforcing the insertion site. Therefore, attachment tubes with region-dependent
and potentially anisotropic material behavior might be advantageous to optimize muscle-bone load transmission after surgery, which may allow lower complication rates and shorter physical recovery.
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Cheng, Man Ying Edith. "Regression modelling of cervical cancer and Chlamydia incidence in the context of national screening programmes." Thesis, University of Southampton, 2009. https://eprints.soton.ac.uk/69712/.
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Prevention of cervical cancer development or reduction in undetected Chlamydia incidence and further onward Chlamydia transmission can be achieved through regular screening. Early detection through a regular screening programme is essential to achieve this goal. A well established screening policy is needed to improve screening efficiency. This PhD study demonstrated the use of mathematical and spatial modelling to explore the risk factors through various regression models, to explore the relation between socio-economic conditions and disease incidence, and also other techniques including classification analysis, decision models, and simulation to evaluate screening options. Based on the risk factors and risk grouping, different groups may have different screening policies. Alternatively, geographical differences can be taken into account by dividing areas into a few parts; the population living in each part may be considered to have different risks of developing cervical cancer or Chlamydia in their life time. Therefore, different screening programmes and services could be provided to those populations according their location or the risk groups which they belong to.
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Zhang, Zhouwei. "Investigation of DNA and RNA markers by novel technologies demonstrates DNA content intratumoral heterogeneity and long non-coding RNA aberrations in breast tumors." ScholarWorks @ UVM, 2014. https://scholarworks.uvm.edu/graddis/323.
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BACKGROUND:
Breast cancer is the most commonly diagnosed cancer and second leading cancer death cause among females in the U.S.A. About 1 in 8 women in U.S will develop invasive breast cancer over the course of her lifetime. In 2013, 234,580 new invasive breast cancer cases are expected to occur in women within the US and approximately 64,640 non-invasive carcinomas in situ were diagnosed in 2013, most of which were ductal carcinoma in situ (DCIS). Along with technological advances, a wide variety of candidate biomarkers have been proposed for cancer diagnosis and prognosis, including DNA content and non-coding RNA. Current techniques for detecting DNA content abnormalities in formalin-fixed, paraffin-embedded (FFPE) tissue samples by flow cytometric analysis have used cells recovered from ≥50µm whole tissue sections. Here, in our first study, a novel core punch sampling method was investigated for assessing DNA content abnormalities and intratumoral heterogeneity in FFPE specimens. Secondly, long non-coding RNAs (lncRNAs) has been examined. LncRNA participates in a broad spectrum of biological activities by diverse mechanisms and its dysregulation is associated with tumorgenesis. Some lncRNAs may function as oncogenes (O) and others as tumor suppressor genes (TSG). To date, lncRNA has been investigated primarily by qRT-PCR and RNA sequencing. This study has examined the relationship of lncRNA expression patterns to breast tumor pathology by chromogenic in situ hybridization (CISH).
METHODS:
Firstly, FFPE breast carcinoma specimens were selectively targeted using 1.0 mm diameter punch needles. Extracted cores were assayed by flow cytometry using a modified-Headley method. Secondly, the lncRNA expression levels of 6 lncRNAs: HOTAIR, H19, KCNQ1OT1, MEG3, MALAT11 and Zfas1, was examined by RNAscope® CISH using FFPE breast tissue microarrays (TMAs) comprising normal adjacent epithelia (NA), DCIS, and invasive carcinoma (IC) from 46 patients. LncRNA associate polycomb complex protein EZH2 was evaluated by immunohistochemistry (IHC). LncRNA data was also compared to standard breast tumor data including ER, PR, Her2 and Ki67 IHC. SYSTAT version 11 statistical package was used to perform for all the tests.
RESULTS:
Following optimization experiments of the core punch flow cytometric approach, DNA index and percent S-phase fraction intratumoral heterogeneities were detected in 10/23 (44%) and 11/23 (47%) specimens respectively. The lncRNA CISH study utilized a TMA that contained 36 spots of NA breast tissues, 34 DCIS spots and 43 IC spots. HOTAIR CISH staining was significantly stronger in IC than DCIS (p
CONCLUSION:
Core-punching is an effective alternative to whole specimen sectioning and shows that macro-level genomic heterogeneity is common even within a single FFPE block. The interrelationship of DNA content heterogeneity to other forms of heterogeneity requires further study. RNAscope CISH supports bright-field microscopy investigations of lncRNA expression in FFPE tissue specimens. HOTAIR, H19 and KCNQ1OT1 may be potential breast cancer biomarkers, both HOTAIR and H19 may be a marker for DCIS at increased risk of progression to invasive cancer. HOTAIR, in particular, may be a predictor for invasive cancer grade.
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LINS, ÉRIKA DE PAULA. "TUTOR, TEACHER OR VIRTUAL SUPPORT?: A STUDY ON THE CONSTRUCTION OF PROFESSIONAL IDENTITY IN THE CONTEXT OF THE DISTANCE EDUCATION." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2016. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=27581@1.
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PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIROCOORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
PROGRAMA DE EXCELENCIA ACADEMICA
A transformação da Educação a Distância nos dias atuais, impulsionada pelas inovações tecnológicas, demanda novas práticas educativas. A interação com os alunos é elemento fundamental nesse processo, tornando a figura do tutor essencial para o desenvolvimento dos alunos. O tutor, entretanto, não possui uma identidade profissional e nem atividades reconhecidas pelas instituições de ensino. Este trabalho teve como objetivo analisar e compreender a identidade profissional dos tutores. Buscou-se identificar o perfil e as percepções desses profissionais sobre o papel que exercem e a definição das atividades de tutoria, partindo de questões como: A identidade do tutor na Educação a Distância se constrói buscando uma aproximação com a docência ou se estabelece no viés burocrático-administrativo?. Quais são as principais características que compõem o perfil do tutor no que se refere aos aspectos gerais e de formação?. Quais são as percepções que o tutor possui acerca do lugar que ele ocupa na Educação a Distância?. Qual a relação entre os documentos oficiais que fazem referência à tutoria no Brasil e a construção da identidade do tutor?. Para responder a estas questões, um questionário foi aplicado para 117 tutores. O questionário foi composto por 23 perguntas fechadas, analisadas com o auxílio do software SPSS, mais duas perguntas abertas, estudadas através da análise de conteúdo. Os resultados revelaram um perfil de tutores especialistas em EAD com outros vínculos de trabalho, que se sentem desvalorizados e se percebem como docentes frente a uma legislação que evidencia o distanciamento entre tutoria e docência.
The modification of the Distance Education today, driven by technological innovation, demands new educational practices. Interaction with students is a key element in this process, making the figure of the tutor essential to the development of students. The tutor, however, does not have a professional identity and activities recognized by educational institutions. This study aims to analyze and understand the professional identity of the tutors. It sought to identify the profile and perceptions of these professionals about their role and the definition of mentoring activities, from questions such as The identity of the tutor in The Distance Education is built by seeking an approach to teaching or is settled in bureaucratic and administrative bias?. What are the main features that compose the tutor s profile with regard to the general aspects and training?. What are the perceptions the tutor has about the his place in Distance Education?. What is the relationship between the official documents the construction of the tutor s identity?. To answer these questions, a questionnaire was applied to 117 tutors. The questionnaire consisted of 23 closed questions, analyzed with the SPSS software, plus two open questions, studied through content analysis. The results revealed a profile of expert tutors in Distance Education with other professional work, a tutor who feels devalued and they perceive themselves as teachers concerning to legislation. The study points to the gap between mentoring and teaching.
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Ramachandran, Niraj. "Corona Ion Deposition: A Novel Non-Contact Method for Drug and Gene Delivery to Living Systems." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002474.
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Твердохлєбова, Наталя Євгеніївна, and Наталія Сергіївна Євтушенко. "Нові можливості викладача-тьютора дистанційного навчання." Thesis, ГО "СФБЖДЛ", 2016. http://repository.kpi.kharkov.ua/handle/KhPI-Press/29118.
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Серед найсучасніших освітніх технологій, що активно розвиваються і поширюються, особливе місце займають дистанційні технології навчання. Завдання сучасного викладача-тьютора – не стільки надати студенту знання відповідно затвердженого навчального плану, але і забезпечити його життєво важливими навичками роботи з інформацією, умінням ефективно взаємодіяти з колегами, в тому числі через Інтернет, а також постійно розвиватися і вчитися самостійно.Among the modern educational technologies that are being actively developed and distributed, distance learning technology take a special place. The task of the modern teacher-tutor is not only to give the student knowledge in accordance with the approved curriculum, but also to provide him vital skills information, the ability to communicate effectively with colleagues, including through the Internet, and continuously develop and study independently.
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Portugal, Laís Maroni. "Avaliação da eficácia antitumoral e toxicidade de lipossomas pH-sensíveis de circulação prolongada contendo cisplatina no tratamento de camundongos portadores de tumor ascítico de Ehrlich." reponame:Repositório Institucional da FIOCRUZ, 2012. https://www.arca.fiocruz.br/handle/icict/4290.
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FAPEMIG: Fundação de Amparo à Pesquisa do Estado de Minas Gerais CPqRR/FIOCRUZ: Centro de Pesquisas René Rachou/Fundação Oswaldo Cruz CNPq: Conselho Nacional de Desenvolvimento Científico e Tecnológico
Cisplatina (CDDP) é um dos agentes ativos citotóxicos mais comumente usados no tratamento da carcinomatose peritoneal. A inconveniência de seu uso clínico são os efeitos colaterais sistêmicos, como nefrotoxicidade e mielotoxicidade. Lipossomas pH-sensíveis de circulação prolongada contendo CDDP (SpHL-CDDP) foram desenvolvidos por nosso grupo de pesquisa com o objetivo de promover a liberação de CDDP mais próximo do tumor, bem como diminuir a toxicidade. O objetivo deste estudo foi avaliar a eficácia antitumoral e toxicidade de SpHL-CDDP, após a administração intraperitoneal em camundongos portadores de tumor nas fases inicial ou avançada, com uma dose de 12 mg/Kg. A sobrevida foi monitorada e amostras de sangue foram coletadas para análises bioquímicas e hematológicas. Rins, fígado e baço foram removidos para exame histopatológico. As células tumorais foram avaliadas, segundo sua viabilidade e ciclo celular. Os resultados demonstraram que a sobrevida de animais tratados com SpHL-CDDP foi maior do que aqueles tratados com CDDP livre. A morte celular causada pelo tratamento com SpHL-CDDP ocorreu através da indução de apoptose com a parada do ciclo celular na fase G0/G1. O tratamento de camundongos que apresentam câncer inicial com ambas as formulações provocou a supressão de granulócitos. Camundongos tratados com CDDP livre apresentaram também diminuição da contagem de plaquetas, o que sugere alta mielotoxicidade. No modelo de câncer avançado, o tratamento com SpHL-CDDP permitiu melhoria da resposta imune. Camundongos portadores de câncer em estágio inicial e tratados com CDDP livre ou SpHL-CDDP apresentaram menor índice de uréia/creatinina, em comparação ao grupo controle salina. Esses achados indicam que ambos os tratamentos foram capazes de reduzir o dano renal causado por carcinomatose peritoneal. A análise microscópica dos rins de camundongos tratados com SpHL-CDDP mostrou alteração morfológica discreta, enquanto necrose tubular foi observada para animais tratados com CDDP livre. Em relação à hepatotoxicidade, nenhuma alteração nos parâmetros de química clínica foi observada. Estes achados revelam que SpHL-CDDP pode melhorar a eficácia antitumoral e diminuir a toxicidade renal e da medula óssea. A dosagem de VEGF no líquido ascítico mostrou que ambas as formulações contendo CDDP, em ambos os estágios de tratamento, diminuíram a capacidade angiogênica do tumor de Ehrlich, apresentando efeito antitumoral. O estudo imunológico mostrou que o tratamento com CDDP livre ou SpHLCDDP apresenta um perfil modulado de resposta imune, com diminuição das citocinas próinflamatórias e de citocinas reguladoras. Portanto, estes resultados abrem a possibilidade de uso futuro de SpHL-CDDP para o tratamento da carcinomatose peritoneal
Cisplatin (CDDP) is one of the most active cytotoxic agents commonly used on treatment of peritoneal carcinomatosis. The inconvenience of its clinical use is systemic side effects, such as nephrotoxicity and myelotoxicity. Long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP) were developed by our research group in order to promote the release of CDDP near the tumor as well decrease of its toxicity. The aim of this study was to evaluate the antitumor efficacy and toxicity of SpHL-CDDP after intraperitoneal administration in initial or disseminated tumor bearing mice, at a dose of 12 mg/Kg. The survival was monitored and blood samples were collected for biochemical and hematological analysis. Kidney, liver and spleen were removed to histopathological examination. Tumor cells were evaluated according to their viability and cell cycle. The survival of animals treated with SpHCDDP was higher than those treated with free CDDP. The cell death caused by treatment with SpHL-CDDP occurred through induction of apoptosis with a cell cycle arrest at G0/G1 phase. The treatment of mice presenting initial cancer with both formulations provoked a suppression of granulocytes. Mice treated with free CDDP showed also a decrease of platelets count, which suggests a high myelotoxicity. Mice affected by cancer at an early stage and treated with free CDDP or SpHL-CDDP showed lower urea/creatinine index as compared to the saline control group. These findings indicate that both treatments were able to reduce the renal damage caused by peritoneal carcinomatosis. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed a discrete morphological alteration, while tubular necrosis was observed for free CDDP treated mice. Concerning hepatotoxicity, no alteration in clinical chemistry parameters was observed. These findings reveal that SpHL-CDDP can improve the antitumor efficacy and decrease renal and bone marrow toxicity. VEGF levels in ascitic fluid showed that both formulations containing CDDP administered in both development stages, decreased angiogenic capacity of Ehrlich tumor, showing their antitumor effect. The immunological study showed that treatment with free CDDP or SpHL-CDDP presents an immune response modulated profile, with reduction of pro-inflammatory and regulatory cytokines. Overall, the results presented in this thesis indicate a promising future application of SpHL-CDDP to peritoneal carcinomatosis treatment.
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Stather, David [Verfasser], Hans-Dieter [Akademischer Betreuer] Volk, Ulrich [Akademischer Betreuer] Keilholz, and Andreas [Akademischer Betreuer] Kaufmann. "Prevalence of possible immune resistance mechanisms of acute leukemias within the context of vaccination strategies using the Wilms tumor gene-1 (WT1) / David Stather. Gutachter: Hans-Dieter Volk ; Ulrich Keilholz ; Andreas Kaufmann." Berlin : Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://d-nb.info/1025708245/34.
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Boquete, Vilarino Lorena. "Development of shRNA screens to identify effectors of three complex traits : neighbour suppression of tumour growth and proliferation and protection from lipotoxicity in β-cells." Thesis, University of Exeter, 2016. http://hdl.handle.net/10871/27635.
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RNA interference (RNAi) is a natural mechanism of cellular defence against exogenous double stranded RNA (dsRNA). The discovery of small dsRNA molecules which can be processed by the RNAi pathway in mammalian cells was one of the key advances in the study of functional genomics. These molecules can be designed to downregulate the expression of specific genes. Collections or libraries of dsRNA molecules targeting an extensive number of genes are now available. Using these libraries, numerous studies have implemented high-throughput screens for the study of molecular effectors of numerous phenotypes. The process of designing an RNAi screen requires the consideration of several critical factors during both the experimental and analysis phases. The experimental screen should aim to reproduce the biological phenomenon studied as closely as possible by choosing an adequate model and screening conditions. Phenotype evaluation and assessment of knockdown effects need careful consideration. The results obtained from large-scale RNAi screens are often complex. An analysis pipeline should be implemented which integrates the biological basis of the phenomenon and facilitates the interpretation of the data. This project designed and implemented an unbiased shRNA screen in two in vitro models relevant to carcinogenesis and diabetes. The first screen implemented used a model of neighbour suppression to study the molecular effectors of the response in tumorigenic cells to growth suppression cues from the surrounding tissue, a cellular interaction relevant in early tumorigenesis. The second screen studied two phenotypes relevant to diabetes: proliferation and resistance to lipotoxicity of β-cells in a reversibly immortalised cell line. An integrative analysis pipeline was also developed to apply network biology and functional enrichment analysis methods for the interpretation of the data obtained from both screens.
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Noirey, Nadège. "Activités fonctionnelles des cellules de Langerhans après contact avec des allergènes respiratoires : étude dans un modèle in vitro utilisant des cellules générées à partir de précurseurs CD34+ isolés du sang de cordon." Lyon 1, 2001. http://www.theses.fr/2001LYO1T130.
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Edvardsson, Tanja. "Consequences of brain tumours from the perspective of the patients and of their next of kin." Doctoral thesis, Örebro universitet, Hälsoakademin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-1742.
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A disease has consequences not only for the afflicted person but also for those who interact with him or her. A low-grade glioma is a brain tumour whose regarding its psychosocial implications for adult patients and their next of kin has received little attention in the literature. In the light of this the overall aim of the present thesis was to provide increased knowledge about how patients with low-grade glioma and their next of kin experience and deal with everyday life. The methods of the studies were mainly qualitative. Thirty-nine patients and 28 next of kin were interviewed and all except one next of kin completed a quality of life questionnaire. The onset of low-grade glioma was described from the patients’ perspective as a process, either rapid (up to a few months) or prolonged over several years. This phase of low-grade glioma encompassed repeated visits to physicians and care institutions. The onset of low-grade glioma was accompanied by stress, anxiety and uncertainty in the case of both the patients and those nearest. The symptoms and problems the patients experienced covered a broad range of consequences, physical, psychological and social. The patients presented a wide range of ways to cope with illness-related problems. The next of kin were often deeply involved in the patients’ situation and many of them experienced extremely stressful emotions mainly in the early period of the illness. They had experience of positive encounters in health care but more often they had had a sense both of powerlessness and of being invisible and neglected. Relations and roles changed in ways that mostly were experienced as negative. Enabling strength in everyday life had to do with alleviation of strain and having a positive outlook upon life. By means of the questionnaire Subjective estimation of Quality of Life (SQoL) the patients and those nearest estimated their quality of life as being comparatively high. Only one variable, among the patients the absence of work/meaningful occupation and among the next of kin the absence of own children, being estimated at below 60% of the maximum score.
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Weigand, Luise [Verfasser], Heinrich H. D. [Akademischer Betreuer] Meyer, and Angela [Akademischer Betreuer] Krackhardt. "Characterization of human MHC II-restricted T cell receptors with reactivity against B cells and tumor cells for therapeutic application in the context of adoptive T cell transfer of transgenic CD4 T cells / Luise Weigand. Gutachter: Angela Krackhardt ; Heinrich H. D. Meyer. Betreuer: Heinrich H. D. Meyer." München : Universitätsbibliothek der TU München, 2011. http://d-nb.info/1016727798/34.
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Melo, Francisco Ramos de. "Modelo neural por padrões proximais de aprendizagem para automação personalizada de conteúdos didáticos." Universidade Federal de Uberlândia, 2012. https://repositorio.ufu.br/handle/123456789/14309.
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This study presents a model for the organization of educational content customized for environments of individual studies. For many students the availability of content in general form can not be efficient. It proposed a multilevel structure of concepts to provide the development of different combinations to show the same content. The work shows that it is possible to customize the content in order to encourage other students with the use of proximal learning standards. These patterns are obtained from the analysis of the action of students with positive results in the individual organization of the content. The formal representation establishes the definition of the student profile, multi-level content, the distribution plan of correction of concepts and teaching career. The structure of the trajectory of student teaching is formally established by the method of finite differences. The system uses artificial intelligence techniques to organize and personalize content reactively. Customization is provided by an artificial neural network that enables the classification of the student profile and assign that profile to a standard proximal learning. To mediate and adjust the contents of a reactive system was inserted into a set of rules from experts in teaching. The experiment showed the applicability and appropriateness of the proposed model. The results indicated the suitability of the approach by automating the organization\'s custom content so adaptive and reactive. The intelligent system to establish the structure of the custom content to be presented was considered efficient, giving the student a better use of the content, with higher and lower final average study time and content presented.Este trabalho apresenta uma modelagem para a organização personalizada de conteúdos didáticos para ambientes de estudos individuais. Para muitos estudantes a disponibilização do conteúdo em formato generalizado pode não ser eficiente. É proposta uma estrutura multinível de conceitos para proporcionar o desenvolvimento de diferentes combinações para a apresentação do mesmo conteúdo. O trabalho mostra que é possível personalizar o conteúdo de forma a favorecer outros estudantes com o uso de padrões proximais de aprendizagem. Estes padrões são obtidos da análise da ação de estudantes, com resultados positivos na organização individual do conteúdo. A representação formal estabelece a definição do perfil do estudante, o conteúdo multinível, o plano de distribuição dos conceitos e a correção da trajetória didática. A estruturação da trajetória didática do estudante é formalmente estabelecida pelo método das diferenças finitas. O sistema utiliza técnicas de inteligência artificial para organizar e personalizar reativamente o conteúdo. A personalização é proporcionada por uma rede neural artificial que possibilita a classificação do perfil do estudante e associa esse perfil a um padrão proximal de aprendizagem. Para mediar e ajustar o conteúdo de forma reativa foi inserido no sistema um conjunto de regras de especialistas em docência. O experimento realizado mostrou a aplicabilidade e a adequação da modelagem proposta. Os resultados indicaram a adequação da abordagem, automatizando a organização personalizada do conteúdo de forma adaptativa e reativa. O sistema inteligente ao estabelecer a estruturação personalizada do conteúdo a ser apresentado foi considerado eficiente, proporcionando ao estudante um melhor aproveitamento do conteúdo, com maior média final e menor tempo de estudo e conteúdo apresentado.
Doutor em Ciências
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Al-Majid, Sadeeka. "Effect of resistance exercise training on muscle mass and protein content in tumor-bearing mice." 2000. http://www.library.wisc.edu/databases/connect/dissertations.html.
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Hsien-ChingHuang and 黃獻慶. "Effects of memantine and cholesterol content on electroporation-induced currents in pituitary tumor GH3 cells." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/03401233722352088655.
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碩士國立成功大學
生理學研究所
100
Membrane electroporation (MEP) is recognized to exert an increase in the electrical conductivity and permeability of the plasma membrane by use of an externally applied electrical field. Owing to an increase in the transmembrane potential, nanoscale pores can form in the cell membrane, thus allowing molecules to be transported into and out of the cells. Memantine (MEM), a derivative of amantadine, is recognized as an antiviral agent. Previous study indicates that changes in the amount of membrane cholesterol can directly modify the activity of membrane ion channels and membrane properties. The electrical and pharmacological properties of MEP-induced inward current (IMEP) remain largely unknown. In this study, we attempted to use the patch-clamp technique to investigate the properties of IMEP. When cell membrane hyperpolarized, an irregular and transient inward current (IMEP) was clearly elicited. Either LaCl3- (300 μM) or MEM (300 μM) could block this current. In whole cell recording, MEM did not exert any effect on voltage-gated Ca2+ current. In inside-out configuration, MEM applied to either external or internal surface of the excised patch did not suppress the activity of ATP-sensitive K+ channels expressed in GH3 cells. In another series of experiments, our data was showed that depletion of membrane cholesterol by exposing cells to HPCD resulted in reduction of IMEP density. Our study provides the first evidence to show that MEM directly inhibits the amplitude of IMEP in pituitary GH3 cells. MEM-mediated block of IMEP in these cells is unlinked to its inhibition of glutamate-induced currents or ATP-sensitive K+ currents. Deplete of membrane cholesterol by HPCD can alter the pore formation, thereby decreasing the IMEP magnitude. The inhibition of MEM and depletion cholesterol in IMEP might be related to cell function.
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Li, Shao-Ti, and 李紹禔. "Contact Force Analysis of Immune Cell and Tumor Cell." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/20393512348084412186.
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碩士國立成功大學
醫學工程研究所碩博士班
92
Fas-L(Fas Ligand：APO-1/CD95) is a member of tumor necrosis family. The regulation system of Fas/Fas-L exits not only in activated T cells and NK cells. Fas-L is found to express on several kinds of tumor cells. The expression of Fas-L on tumor cell induces apoptosis of immune cell, and the dispersion and migration of tumor cellular mass center occurs when tumor cells are affected by infiltration of immune cells. The mechanism of contact communication between tumor and immune cell leading to obvious difference of tumor structural change is unknown. This study takes advantage of laser tweezers and cyto-detachment mechanism to measure the interaction force of tumor and immune cells with designed time lag. The research is executed with human glioma cell line and leukemia cell line -Jurkat cell. U-118MG(R) of low Fas-L expression suppressed by ribozyme and U-118MG(V) of normal Fas-L expression are tested. This study aims at investigation of the contact force variation between immune cell and tumor cell through mechanical analysis and elucidates the factors of contact influence of immune cell and glioma cell in cell mechanics. The result shows that adhesion level between Jurkat and U-118MG(V) is a little higher than that between Jurkat and U118MG(R). It is likely caused by binding force of Fas/Fas-L activation or adhesiveness change. As for the adhesion of glioma, the adhesiveness of U-118MG(R) is higher than that of U-118MG(V). It may be responsible for the scattering of U-118MG(V) and the concentration mass of U-118MG(R) observed in nude mice. After 12 hours co-cultured with Jurkat, the adhesion property of U-118MG(V) is reduced obviously. It could be the effect of Jurkat contact, but further research is required.
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Chen, I.-Hui, and 陳憶慧. "A Mathematics Tutor How to Improve her Technology, Pedagogical and Content Knowledge." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/frjnxn.
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碩士國立中央大學
學習與教學研究所
105
In this study, action narrative inquiry was adopted to explore how a mathematics tutor in the shadow education develop professional learning community (PLC) and technology, pedagogical and content knowledge (TPACK) in the instructional practice by technologies. The data were collected by using records of PLC’s meeting, notes of online-PLC, course videos, and teacher’s teaching daries. A math tutor used technology integrated into instruction which had four stages, such as forming period, constructive period, practice period, and reflection period. In the froming period, teachers formed professional learning community awareness. PLC constructed TPACK knowledge through teachers’ dialogues and PLC’s knowledge base became the most important instructional resource in constructive period. Third, a math tutor practice TPACK in teaching, such as distance education, electronic whiteboard into one-on-two teaching, physical and virtual mixing course. Finally, a math tutor reflected and adjusted the instructional program through students、parents and peer teachers’ feedback. The key findings of this study are as follows. 1. The community knowledge base covered TPACK was an important resource for the professional development for a math tutor. 2. PLC’s physical meeting promoted the trust and relationship between teachers by giving immediate instructional feedback. 3. For teaching each students well, a tutor should take turn to teach 10th grade students by interactive whiteboard in one-on-two class. 4. The 9th grade student had high satisfaction due to the pressure form study, and technological tool became necessary in the class. 5. For 8th grade student who needed to be instructed math and science, the tutor adpoted on-line class to add class hours, but the student couldn’t learn well. And then, the tutor adopted on-line messages to solve her subjects’ problems and her parents monitored her learning process that helped her preform stably in the school. In summary, a mathematics tutor wants to integrate technology into instruction effectively should consider students’ need to adjust instructional skill.
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Ying-Ru, Lin, and 林映如. "A Study on the Contents of Competency for Online-tutor." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/30193296636180574613.
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碩士國立臺灣師範大學
科技應用與人力資源發展學系
99
This study was aimed to explore the contents of competency for Online-tutor. According to the purpose, it can further to scheme the strategy for incubating teacher and improve self and professional development. Through the research process, the literatures review and Delphi technique were adopted to attain the Online-tutor competency indicators which included 3 categories, 11 dimensions and 73 items. The Online-tutor competency indicators' categories, dimensions as follows: The categories of Online-tutor competency indicators include educational knowledge, professional attitude and personal interaction, and information literacy. The dimensions of Online-tutor competency indicators include: teaching competence, subject knowledge, curricular knowledge, collecting information, behavior management, communication competence, teaching belief philosophy, internet-based education, digital teaching, software and hardware application competence, information retrieval and management competence. Finally, provides recommendations for education administration, teacher cultivation institution, Online-tutors, and future studies.
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Mauricio, Ian Paolo Morelos. "Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway." Thesis, 2018. https://hdl.handle.net/2144/31243.
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The Hippo tumor suppressor pathway is a highly conserved signaling cascade initially identified in Drosophila which acts to regulate organ size and cellular proliferation. The Hippo pathway integrates extracellular and intracellular cues such as cytoskeletal tension, growth factor signaling, and nutrient availability to ultimately activate the LATS kinases. Activated LATS kinases then inhibit the downstream oncoproteins YAP and TAZ via a phosphorylation-dependent mechanism, in which 14-3-3 dependent cytoplasmic sequestration promotes YAP/TAZ degradation via the ubiquitin-proteasome pathway.
Upstream regulators of LATS activation remain poorly characterized. MST1/2, which are mammalian orthologs of the Drosophila Hpo kinase, appear to be largely dispensable for Hippo pathway activation, suggesting evolutionary redundancy arising as a result of divergence and diversification of MSTs in human cells. We identified MST4, a close cousin of MST1/2, as a potential novel regulator of Hippo signaling in non-transformed, non-polarized human cells. Loss of MST4 resulted in decreased YAP phosphorylation in response to actin disruption, and also increased total abundance of TAZ, but interestingly did not affect levels of phosphorylated LATS. Overexpression of wild-type MST4 activated Hippo signaling and promoted TAZ degradation, which correlated to the effects MST4 had on levels of HIF1α. MST4 may be playing a previously unappreciated role in regulation of Hippo tumor suppressor signaling via a LATS1/2-independent pathway.
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Pike, Robert Neil. "A study of the proteinase, cathepsin L, in the context of tumour invasion." Thesis, 1990. http://hdl.handle.net/10413/9536.
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The proteinase, cathepsin L, has been strongly implicated in the processes of tumour invasion and metastasis. A new purification method, three-phase partitioning, characterised in terms of the parameters which affected its fractionation of proteins, was found to simplify the purification of cathepsin L from sheep liver. This method, together with a novel cation-exchange step on S-Sepharose and molecular exclusion chromatography, enabled the enzyme to
be purified to homogeneity, in a single-chain form. A further enzyme fraction was isolated as a proteolytically active complex with the endogenous inhibitor of cysteine proteinases, cystatin. Studies on the proteolytically active
complex revealed that approximately 60% of it was covalently bound and proteolytically active, while the other 40% was non-covalently bound and proteolytically inactive, in the manner normally found for the binding of cystatin to cysteine proteinases. A cystatin fraction from sheep liver containing variants of cystatin B, was shown to be able
to form complexes with free cathepsin L in vitro in a pH-dependent, rapid process, which was mildly stimulated by a reducing agent. Cathepsin L was also isolated from human spleen, but only as a protcolytically inactive complex, presumably also with cystatin(s). The complexed and free cathepsin L from sheep liver were analysed for their pH-dependent characteristics, and it was found that both forms of the enzyme were more active and stable at, or near, neutral pH, than would have been expected from published values. Specific polyclonal antibodies to pure sheep cathepsin L were raised in rabbits and chickens. The chicken egg yolk antibodies were of a much higher titre and were immunoinhibitory towards the enzyme, which the rabbit antibodies were not. Anti-peptide antibodies, raised in rabbits against a peptide sequence selected from the active site of human cathepsin L, were highly specific for cathepsin L and immunoinhibitory towards the enzyme. Together with the polyclonal anti-cathepsin L antibodies, they show promise for immunoinhibitory and immunocytochemical studies on the enzyme, and as potential anti-tumour
drugs.Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1990.