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The Global ETD Search service is a free service for researchers
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Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 21 to 27 of 27 (0.046 seconds)| 21 |
Hepatitis C virus infection : a nationwide study of associated morbidity and mortalityDuberg, Ann-Sofi January 2009 (has links)
The hepatitis C virus (HCV) was characterised in 1989. HCV was transmitted through transfusion of blood/blood products, but injection drug use is now the most common route of transmission. The infection is usually asymptomatic but becomes chronic in about 75%, and in 20 years 15-25% develops liver cirrhosis, with a risk for liver failure and liver cancer. HCV has also been associated with lymphoproliferative disorders. The aim of this thesis was to study morbidity and mortality in a national, population-based cohort of HCV-infected individuals. The study population consisted of all persons with a diagnosed HCV-infection recorded in the national surveillance database. This file was linked to other national registers to obtain information of emigration, deaths, cancers, and inpatient care. All personal identifiers were removed before analysis. In Paper I the standardized incidence ratios (SIR) for Hodgkin’s and non-Hodgkin’s lymphoma (NHL), multiple myeloma, acute and chronic lymphatic leukaemia, and thyroid cancer were studied. In the HCV-cohort (n: 27,150) there was a doubled risk for NHL and multiple myeloma in patients infected for more than 15 years, compared with the general population (age-, sex- and calendar-year specific incidence rates). The results strengthened these earlier controversial associations. The SIR and also the absolute risk for primary liver cancer were estimated in Paper II. In the HCV-cohort (n: 36,126) the individuals infected for more than 25 years had a more than 40 times increased risk for liver cancer compared with the general population. The absolute risk of primary liver cancer was 7% within 40 years of HCV-infection. Mortality and cause of death were studied in Paper III. The standardized mortality ratio (SMR) demonstrated a 5.8 times excess mortality in the HCV-cohort (n: 34,235) compared with the general population, and a 35.5 times excess mortality from liver disease. Deaths from illicit drugs and external reasons were common in young adults. Paper IV presents a study of inpatient care. The HCV-cohort (n: 43,000) was compared with a matched reference population (n: 215,000). Cox regression was used to estimate the likelihood, a hazard ratio, for admission to hospital, and frequencies and rates to estimate the total burden. In the HCV-cohort inpatient care was high and about 50% was psychiatric, often drug-related care. The likelihood for liver-related admissions was very high, and serious liver complications increased in the 2000s, indicating that HCV-associated liver disease will increase the next decade. In the 2000s, about 1000 individuals per year were treated with HCV-combination therapy. To conclude, the risk for NHL and multiple myeloma was doubled, and liver- and drug-related morbidity and mortality was very high in the HCV-cohort. Serious liver complications increased in the 2000s and will probably increase the coming decade.
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Étude de l'activité anti-cancéreuse du PCK3145, un peptide dérivé de PSP-94, sur les cancers hématologiquesGuérin, Mireille 08 1900 (has links)
Le PCK3145 est un peptide de 15 acides aminés inhibant la sécrétion de MMP-9 et
démontrant une activité anti-tumorale contre le cancer de la prostate. Comme les
cancers hématologiques sécrètent MMP-9, nous avons donc évalué l’effet du PCK3145
sur ces cancers. Nous avons démontré que les lignées humaines de lymphome non-
Hodgkinien (LNH) SR et de myélome multiple RPMI-8226 ainsi que la lignée murine
de mastocytome P815 ont une prolifération réduite suite à une exposition au PCK3145.
Ce peptide diminue également la clonogénicité de ces cellules. In vivo, le PCK3145 diminue significativement la croissance des tumeurs sous-cutanées P815 comparativement au PBS (p<0.001) et aux peptides contrôles (« scrambled peptide » (p<0.05) et PCK5266 (p<0.01)). De plus, le traitement au PCK3145 diminue le nombre de métastases au niveau du foie par rapports aux contrôles (p<0.05). Les niveaux de MMP-9 dans le sang des souris traitées au PCK3145 sont similaires à ceux dans le sang
des souris sans tumeur. Par contre, chez les souris recevant le PBS ou le « scrambled
peptide », les niveaux de MMP-9 étaient significativement plus élevés que dans les
souris sans tumeur et les souris traitées au PCK3145 (p<0.05). De surcroît, dans un
modèle de xénogreffe, le PCK3145 diminue significativement la croissance des
lymphomes SR par rapport au PBS (p<0.01) et au « scrambled peptide » (p<0.001). Ces
résultats indiquent que le PCK3145 possède une activité anti-tumorale et pourrait
représenter un agent intéressant pour le traitement de plusieurs cancers hématologiques. / PCK3145 has been shown to exert anti-tumor activity against prostate cancer cells. In a
Phase I clinical study, this peptide demonstrated low toxicity. To determine whether PCK3145 could exert cytotoxic activity against other marrow infiltrating cancers, we tested its activity against hematologic cancers. Interestingly, PCK3145 inhibited the proliferation of human NHL (SR) and myeloma (RPMI-8226) cell lines and murine mastocytoma (P815) cell line in vitro. Moreover, PCK3145 reduced the clonogenicity of these cell lines. To explore its activity in vivo, DBA/2 mice were injected with P815 cells. PCK3145 treatment significantly decreased P815 tumors growth in comparison to PBS (p<0.001), scrambled peptide (p<0.05) and PCK5266 (amino acids 52-66 of PSP-94) (p<0.01). Intraperitoneal PCK3145 treatment led to a decreased number of liver
metastasis compared to PBS (p<0.05) and scrambled peptide (p<0.05). MMP-9 levels,
measured by ELISA, in the peripheral blood of treated P815 bearing mice were similar
to those obtained with healthy animals (12.83 1.890 (mean SD) ng/ml and 6.48 0.4070
ng/ml, respectively), while MMP-9 levels were elevated in mice treated with PBS and
scrambled peptide (35.12 8.559 ng/ml and 22.60 3.944 ng/ml, respectively; p<0.05). In
NOD/SCID mice PCK3145 treatment resulted in significant inhibition of human NHL SR growth compared to treatment with PBS (p<0.001) and scrambled peptide (p<0.01).
Consequently, treatment with PCK3145 can reduce tumor cell proliferation of murine
and human hematologic cancers. In addition, PCK3145 has the potential to inhibit
tumor cells dissemination by lowering MMP-9 secretion. Thus, PCK3145 represents a
unique peptide demonstrating sequence-specific anti-tumor activity hematologic
malignancies.
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Étude de l'activité anti-cancéreuse du PCK3145, un peptide dérivé de PSP-94, sur les cancers hématologiquesGuérin, Mireille 08 1900 (has links)
Le PCK3145 est un peptide de 15 acides aminés inhibant la sécrétion de MMP-9 et
démontrant une activité anti-tumorale contre le cancer de la prostate. Comme les
cancers hématologiques sécrètent MMP-9, nous avons donc évalué l’effet du PCK3145
sur ces cancers. Nous avons démontré que les lignées humaines de lymphome non-
Hodgkinien (LNH) SR et de myélome multiple RPMI-8226 ainsi que la lignée murine
de mastocytome P815 ont une prolifération réduite suite à une exposition au PCK3145.
Ce peptide diminue également la clonogénicité de ces cellules. In vivo, le PCK3145 diminue significativement la croissance des tumeurs sous-cutanées P815 comparativement au PBS (p<0.001) et aux peptides contrôles (« scrambled peptide » (p<0.05) et PCK5266 (p<0.01)). De plus, le traitement au PCK3145 diminue le nombre de métastases au niveau du foie par rapports aux contrôles (p<0.05). Les niveaux de MMP-9 dans le sang des souris traitées au PCK3145 sont similaires à ceux dans le sang
des souris sans tumeur. Par contre, chez les souris recevant le PBS ou le « scrambled
peptide », les niveaux de MMP-9 étaient significativement plus élevés que dans les
souris sans tumeur et les souris traitées au PCK3145 (p<0.05). De surcroît, dans un
modèle de xénogreffe, le PCK3145 diminue significativement la croissance des
lymphomes SR par rapport au PBS (p<0.01) et au « scrambled peptide » (p<0.001). Ces
résultats indiquent que le PCK3145 possède une activité anti-tumorale et pourrait
représenter un agent intéressant pour le traitement de plusieurs cancers hématologiques. / PCK3145 has been shown to exert anti-tumor activity against prostate cancer cells. In a
Phase I clinical study, this peptide demonstrated low toxicity. To determine whether PCK3145 could exert cytotoxic activity against other marrow infiltrating cancers, we tested its activity against hematologic cancers. Interestingly, PCK3145 inhibited the proliferation of human NHL (SR) and myeloma (RPMI-8226) cell lines and murine mastocytoma (P815) cell line in vitro. Moreover, PCK3145 reduced the clonogenicity of these cell lines. To explore its activity in vivo, DBA/2 mice were injected with P815 cells. PCK3145 treatment significantly decreased P815 tumors growth in comparison to PBS (p<0.001), scrambled peptide (p<0.05) and PCK5266 (amino acids 52-66 of PSP-94) (p<0.01). Intraperitoneal PCK3145 treatment led to a decreased number of liver
metastasis compared to PBS (p<0.05) and scrambled peptide (p<0.05). MMP-9 levels,
measured by ELISA, in the peripheral blood of treated P815 bearing mice were similar
to those obtained with healthy animals (12.83 1.890 (mean SD) ng/ml and 6.48 0.4070
ng/ml, respectively), while MMP-9 levels were elevated in mice treated with PBS and
scrambled peptide (35.12 8.559 ng/ml and 22.60 3.944 ng/ml, respectively; p<0.05). In
NOD/SCID mice PCK3145 treatment resulted in significant inhibition of human NHL SR growth compared to treatment with PBS (p<0.001) and scrambled peptide (p<0.01).
Consequently, treatment with PCK3145 can reduce tumor cell proliferation of murine
and human hematologic cancers. In addition, PCK3145 has the potential to inhibit
tumor cells dissemination by lowering MMP-9 secretion. Thus, PCK3145 represents a
unique peptide demonstrating sequence-specific anti-tumor activity hematologic
malignancies.
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Expressão do vírus Epstein-Barr em células tumorais do Linfoma de Hodgkin Clássico: correlação com fatores desfavoráveis e sobrevidaMayrink, Graziela Toledo Costa 10 August 2016 (has links)
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Previous issue date: 2016-08-10 / Introdução: A associação entre Linfoma de Hodgkin clássico e o status tumoral do
vírus Epstein- Barr é bem definida. Entretanto, a expressão da positividade do vírus
Epstein-Barr nas células de Reed-Sternberg/Hodgkin e o impacto dessa relação na
sobrevida do Linfoma de Hodgkin clássico permanecem controversos e apresentam
resultados conflitantes em estudos de diversas regiões do mundo. Considera-se
essencial o entendimento fisiopatogênico desse vírus no prognóstico dos pacientes
com Linfoma de Hodgkin clássico. Objetivo: Correlacionar o status do vírus Epstein
Barr com os fatores de risco desfavoráveis e fatores prognósticos do Linfoma de
Hodgkin clássico em uma população brasileira. Métodos: A positividade do vírus
Epstein-Barr foi determinada pelo método de Hibridização in situ para o ácido
ribonucleico viral e pela imuno-histoquímica para proteína de membrana latente viral
1. A revisão histopatológica das amostras e a análise dos testes de identificação
foram realizadas por uma hematopatologista experiente. Avaliou-se o impacto
prognóstico do status do vírus Epstein-Barr em 29 pacientes com Linfoma de
Hodgkin clássico. Os fatores prognósticos do Escore Prognóstico Internacional para
estadio avançado e os fatores de risco desfavoráveis instituídos pelo Grupo Alemão
de Estudos em Hodgkin para estadio limitado foram correlacionados com o status
viral nas células tumorais. Para as associações entre presença do vírus Epstein-Barr
e outras variáveis categóricas, aplicaram-se os testes de Qui-quadrado ou exato de
Fisher. A Sobrevida Global e a Sobrevida Livre de Eventos foram analisadas pelo
método de Kaplain-Meier e Modelo de Regressão Proporcional de Cox. Resultados:
A média de idade ao diagnóstico foi 33 anos. O status do vírus Epstein-Barr nas
células tumorais foi positivo em 37,9%. As células tumorais positivas para o vírus
foram mais frequentes em pacientes com idade maior que 45 anos, sem diferença
estatística. O subtipo celularidade mista foi o mais frequente (p = 0,02) e o tamanho
de efeito desse teste foi de moderada magnitude. Na análise univariada, as
sobrevidas Livre de Eventos e Global não apresentaram significância estatística para
idade, sexo, estadio clínico, hemoglobina, leucocitose, linfocitopenia, albumina,
envolvimento nodal, sintomas B, doença extranodal e doença Bulky entre os
pacientes positivos e negativos para o vírus Epstein-Barr (p > 0,05). Os pacientes
positivos apresentaram maior Sobrevida Livre de Eventos quando comparados aos
pacientes negativos, embora a diferença não apresentasse significância (p = 0,07).
Na análise multivariada, a positividade ao vírus Epstein-Barr não demonstrou fator
prognóstico significante. Conclusões: Apesar do status do vírus Epstein-Barr nas
células tumorais não ter revelado associação com fatores prognósticos adversos e
não ter influenciado a Sobrevida Global e a Sobrevida Livre de Eventos, observou-se
uma associação positiva entre a presença desse vírus e o subtipo celularidade
mista, demonstrando uma relação com o subtipo histológico de pior prognóstico. / Introduction: The association between classical Hodgkin’s Lymphoma and tumor
Epstein-Barr virus status is well established. However, the expression of Epstein-Barr
virus presence in Hodgkin/Reed-Sternberg cells and its prognosis remains
controversial and presentes conflicting results in studies worldwide. Understanding
the pathophysiological role of this virus in the prognosis of patients with classical
Hodgkin’s Lymphoma is essential. Objective: The aim of this study is to correlate the
clinical outcome with Epstein-Barr virus status in a Brazilian population. Methods:
Epstein-Barr virus positivity was determined by in situ hybridization for Epstein-Barr
virus-encoded ribonucleic acid and immunohistochemistry for viral latent membrane
protein-1. The histopathology review and the analysis of identification tests were
performed by an hematopathologist expert. The prognostic impact of Epstein-Barr
virus status in 29 patients with classical Hodgkin’s Lymphoma was evaluated.
Prognostic factors from International Prognostic Score to advanced stage and risk
factors from German Hodgkin Study Group to limited stage were correlated with
tumor cells Epstein-Barr virus status. In order to determine associations between the
presence of Epstein-Barr virus and other categorical variables, Chi-square or Fisher's
exact tests were applied. Overall and event-free survivals were analyzed with
Kaplan-Meier method and Cox proportional hazards regression models. Results: The
mean age at diagnosis was 33 years. Tumor cells Epstein-Barr virus status was
positive in 37.9%. Epstein-Barr virus-positive classical Hodgkin’s Lymphoma was
more frequent in patients older than 45 years, with no statistical difference. Mixed
cellularity histological subtype was more common in Epstein-Barr virus-related tumor
cells (p = 0.02) and its effect-size index was medium. Univariate analysis, event-free
survival and overall survival were not significantly associated to age, sex, clinical
stage, hemoglobin, leukocytes, lymphocytes, albumin, nodal involvement, B
symptoms, extranodal disease and Bulky disease in Epstein-Barr virus-positive and
negative patients (p > 0.05). Epstein-Barr virus-positive patients had longer event
free survival when compared to Epstein-Barr virus-negative ones, even though the
difference was not statistically significant (p = 0.07). In multivariate analysis, Epstein
Barr virus positivity was not a significant prognostic factor. Conclusions: Although the
Epstein-Barr virus status in tumor cells was not associated with adverse prognostic
factors and did not influence the overall and event-free survivals, a positive
association between the presence of Epstein-Barr virus and Mixed-cellularity subtype
was noticed.
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Moving beyond Genome-Wide Association Studies / Comment aller au delà des études d'association à l'échelle du génome entierDelahaye-Sourdeix, Manon 14 November 2014 (has links)
Les études d'association à grande échelle consistent à étudier la corrélation de plusieurs millions de polymorphismes nucléotidiques avec un risque de cancer chez des milliers d'individus, sans avoir besoin de connaissances préalables sur la fonction biologique de ces variants. Ces études ont été utiles pour établir des hypothèses étiologiques et comprendre l'architecture génétique sous-jacente de plusieurs maladies humaines. Cependant, la plupart des facteurs héréditaires de ces maladies restent inexpliqués. Une partie de cette variation pourrait venir de variants rares qui ne sont pas ciblés par les puces de génotypage actuelles ou encore de variants avec un effet plus modéré voire faible pour lesquels une détection par les études d'association actuelles n'est pas envisageable. Dans ce contexte et comme illustré dans cette thèse, les récentes études d'association peuvent maintenant servir de point de départ pour de nouvelles découvertes, en mettant en place des stratégies innovantes pour étudier à la fois les variants rares et les maladies rares. Nous avons plus particulièrement exploré ces techniques dans le cadre du cancer du poumon, des voies aérodigestives et du lymphome de Hodgkins. L'utilisation de la bioinformatique pour combiner les résultats des études avec d'autres sources d'information, l'intégration de différents types de données génomiques ainsi que l'investigation de la relation entre altérations germinales et somatiques représentent les principales opportunités poursuivies dans ce travail de thèse / Genome-wide association (GWA) studies consist in testing up to one million (or more) single nucleotide polymorphisms (SNPs) for their association with cancer risk in thousands of individuals, without requiring any prior knowledge on the functional significance of these variants. These studies have been valuable for establishing etiological hypotheses and understanding the underlying genetic architecture of human diseases. However, most of the heritable factors of these traits remain unexplained. Part of this variation may come from rarer variants that are not targeted by current genotyping arrays or variants with moderate to low effects for which detection by current GWA studies is impractical. In this context and as illustrated in this thesis, GWA studies can now serve as starting points towards further discoveries, looking for new strategies to study both rarer variants and rarer diseases. We have specifically explored these approaches in the context of lung cancer, head and neck cancer and Hodgkin's lymphoma. The use of bioinformatics to combine recent GWA study results with other sources of information, the integration of different types of genomic data as well as the investigation of the interrelationship between germline and somatic alterations represent the main opportunities pursued in this thesis work
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A Pedagogy of Holistic Media Literacy: Reflections on Culture Jamming as Transformative Learning and HealingStasko, Carly 14 December 2009 (has links)
This qualitative study uses narrative inquiry (Connelly & Clandinin, 1988, 1990, 2001) and self-study to investigate ways to further understand and facilitate the integration of holistic philosophies of education with media literacy pedagogies. As founder and director of the Youth Media Literacy Project and a self-titled Imagitator (one who agitates imagination), I have spent over 10 years teaching media literacy in various high schools, universities, and community centres across North America. This study will focus on my own personal practical knowledge (Connelly & Clandinin, 1982) as a culture jammer, educator and cancer survivor to illustrate my original vision of a ‘holistic media literacy pedagogy’. This research reflects on the emergence and impact of holistic media literacy in my personal and professional life and also draws from relevant interdisciplinary literature to challenge and synthesize current insights and theories of media literacy, holistic education and culture jamming.
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A Pedagogy of Holistic Media Literacy: Reflections on Culture Jamming as Transformative Learning and HealingStasko, Carly 14 December 2009 (has links)
This qualitative study uses narrative inquiry (Connelly & Clandinin, 1988, 1990, 2001) and self-study to investigate ways to further understand and facilitate the integration of holistic philosophies of education with media literacy pedagogies. As founder and director of the Youth Media Literacy Project and a self-titled Imagitator (one who agitates imagination), I have spent over 10 years teaching media literacy in various high schools, universities, and community centres across North America. This study will focus on my own personal practical knowledge (Connelly & Clandinin, 1982) as a culture jammer, educator and cancer survivor to illustrate my original vision of a ‘holistic media literacy pedagogy’. This research reflects on the emergence and impact of holistic media literacy in my personal and professional life and also draws from relevant interdisciplinary literature to challenge and synthesize current insights and theories of media literacy, holistic education and culture jamming.
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