Global ETD Search

11	Pregnancy related risk factors for breast cancer / Larfors, Gunnar, January 2004 (has links) Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.
12	Gestação múltipla com mola completa e feto normal coexistente: coorte multicêntrica / Multiple pregnancies with complete mole and coexisting normal fetus: multicenter cohort Lin, Lawrence Hsu 22 November 2017 (has links) Objetivo: Comparar características clínicas e resultados de gestações múltipla com mola completa e feto normal coexistente (MHCFC) no New England Trophoblastic Disease Center (NETDC) e em centros de doença trofoblástica (CDT) brasileiros. Métodos: Coorte retrospectiva composta por pacientes com MHCFC provenientes do NETDC (1966-2015) e quatro CDT brasileiros (1990- 2015). Foram realizadas comparações referentes à localização geográfica (NEDTC vs CDT brasileiros), períodos diferentes no NETDC (1966-1989 vs 1990-2015) e quanto evolução para neoplasia trofoblástica gestacional (NTG). Resultados: No período, foram identificados 12.455 casos de doença trofoblástica gestacional, sendo 72 casos de MHCFC inclusos neste estudo. As características clínicas e resultados foram semelhantes entre os casos dos CDT brasileiros (n=46) e NETDC (n=13) entre 1990 e 2015, com exceção de um número significativamente maior de condições potencialmente letais no Brasil (p=0,046). Não houve diferença quanto à apresentação clínica ou aos resultados em dois períodos diferentes no NETDC (13 casos de 1966-1989 vs 13 casos de 1990-2015). Houve 10 casos de interrupção eletiva da gestação (14% das 70 gestações em que o resultado obstétrico estava disponível) e 36 nascimentos de fetos viáveis (60% das 60 gestações nas quais se optou por conduta expectante). A taxa de NTG foi de 46% (31 de 68 casos em que o resultado quanto evolução para NTG estava disponível); os casos que progrediram para NTG apresentaram níveis mais elevados de gonadotrofina coriônica (250.000 mUI/mL vs 120.000 mUI/mL; p=0,026), menor idade gestacional no término da gravidez (17 semanas vs 28,5 semanas; p < 0,001), menor viabilidade fetal (27% vs 69%; p < 0,001), maior taxa de evolução para abortamento espontâneo (35% vs 9%; p=0,020) e mais interrupções da gestação por conta de intercorrências clínicas graves (26% vs 0%; p=0,003). No entanto, a interrupção eletiva da gestação não teve associação com o desenvolvimento de NTG. Conclusões: A maior diferença regional nas MHCFC foi a presença de mais condições potencialmente letais no Brasil. Quando adotada conduta expectante, houve possibilidade de nascimento de feto viável na maior parte das MHCFC. Foi observada elevada taxa de evolução para NTG em MHCFC. A interrupção eletiva da gravidez não influenciou a progressão para NTG, porém interrupções da gestação por complicações clínicas graves, evolução da gestação para abortamento espontâneo, menor idade gestacional no término da gestação, menor viabilidade fetal e níveis elevados de gonadotrofina coriônica foram associados ao desenvolvimento de NTG em MHCFC / Objective: To determine the clinical characteristics and outcomes of multiple pregnancies with complete mole and coexisting normal fetus (CHMCF) in New England Trophoblastic Disease Center (NETDC) and Brazilian trophoblastic disease centers (BTDC). Methods: Retrospective non-concurrent cohorts comprised of CHMCF from NETDC (1966-2015) and four BTDC (1990-2015). Comparisons were made regarding: geographical location from 1990 to 2015 (NETDC vs BTDC), two different periods of time in NETDC (1966-1989 vs 1990-2015) and patients who developed gestational trophoblastic neoplasia (GTN) with the ones that spontaneously regressed. Results: From a total of 12,455 cases of gestational trophoblastic disease seen at the referral centers, 72 CHMCF were identified. Clinical characteristics and outcomes were similar between BTDC (n=46) and NETDC (n=13) from 1990 to 2015, apart from a much higher frequency of potentially life-threatening conditions in Brazil (p=0.046). There were no significant changes in the clinical presentation or outcomes in two different time periods in NETDC (13 cases in 1966-1989 vs 13 cases in 1990-2015). Ten pregnancies were electively terminated (14% of 70 cases with available obstetric outcome) and 36 resulted in viable live infants (60% of 60 pregnancies that were expectantly managed). The rate of GTN was 46% (31 out of 68 cases with available information on GTN development); the cases that progressed to GTN presented with higher chorionic gonadotropin levels (250.000 mIU/mL vs 120.000 mIU/mL; p=0.026), lower gestational age at the end of pregnancy (17 weeks vs 28,5 weeks; p < 0,001), lower fetal viability (27% vs 69%; p < 0,001), higher rate of spontaneous abortions (35% vs 9%; p=0.020) and higher frequency of termination of pregnancy due to medical complications (26% vs 0%; p=0.003) when compared to those with spontaneous remission. However, elective termination of pregnancy was not associated with GTN development. Conclusions: The main regional difference in CHMCF was related to a higher rate of potentially life-threatening conditions in Brazil. Most of the women with CHMCF who were managed expectantly delivered a viable fetus. CHMCF exhibited a high GTN rate. Elective termination of pregnancy did not influence the risk for GTN; however the need for termination due to severe medical complications, spontaneous abortions, lower gestational age at the end of pregnancy, lower fetal viability and higher hCG levels were associated with GTN progression in CHMCF Doença trofoblástica gestacional Gestational trophoblastic disease Gravidez de gêmeos Gravidez múltipla Hydatidiform mole Mola hidatiforme Near miss Near miss healthcare Neoplasia trofoblástica gestacional Pregnancy twin Pregnancy multiple Trophoblastic neoplasms
13	Gestação múltipla com mola completa e feto normal coexistente: coorte multicêntrica / Multiple pregnancies with complete mole and coexisting normal fetus: multicenter cohort Lawrence Hsu Lin 22 November 2017 (has links) Objetivo: Comparar características clínicas e resultados de gestações múltipla com mola completa e feto normal coexistente (MHCFC) no New England Trophoblastic Disease Center (NETDC) e em centros de doença trofoblástica (CDT) brasileiros. Métodos: Coorte retrospectiva composta por pacientes com MHCFC provenientes do NETDC (1966-2015) e quatro CDT brasileiros (1990- 2015). Foram realizadas comparações referentes à localização geográfica (NEDTC vs CDT brasileiros), períodos diferentes no NETDC (1966-1989 vs 1990-2015) e quanto evolução para neoplasia trofoblástica gestacional (NTG). Resultados: No período, foram identificados 12.455 casos de doença trofoblástica gestacional, sendo 72 casos de MHCFC inclusos neste estudo. As características clínicas e resultados foram semelhantes entre os casos dos CDT brasileiros (n=46) e NETDC (n=13) entre 1990 e 2015, com exceção de um número significativamente maior de condições potencialmente letais no Brasil (p=0,046). Não houve diferença quanto à apresentação clínica ou aos resultados em dois períodos diferentes no NETDC (13 casos de 1966-1989 vs 13 casos de 1990-2015). Houve 10 casos de interrupção eletiva da gestação (14% das 70 gestações em que o resultado obstétrico estava disponível) e 36 nascimentos de fetos viáveis (60% das 60 gestações nas quais se optou por conduta expectante). A taxa de NTG foi de 46% (31 de 68 casos em que o resultado quanto evolução para NTG estava disponível); os casos que progrediram para NTG apresentaram níveis mais elevados de gonadotrofina coriônica (250.000 mUI/mL vs 120.000 mUI/mL; p=0,026), menor idade gestacional no término da gravidez (17 semanas vs 28,5 semanas; p < 0,001), menor viabilidade fetal (27% vs 69%; p < 0,001), maior taxa de evolução para abortamento espontâneo (35% vs 9%; p=0,020) e mais interrupções da gestação por conta de intercorrências clínicas graves (26% vs 0%; p=0,003). No entanto, a interrupção eletiva da gestação não teve associação com o desenvolvimento de NTG. Conclusões: A maior diferença regional nas MHCFC foi a presença de mais condições potencialmente letais no Brasil. Quando adotada conduta expectante, houve possibilidade de nascimento de feto viável na maior parte das MHCFC. Foi observada elevada taxa de evolução para NTG em MHCFC. A interrupção eletiva da gravidez não influenciou a progressão para NTG, porém interrupções da gestação por complicações clínicas graves, evolução da gestação para abortamento espontâneo, menor idade gestacional no término da gestação, menor viabilidade fetal e níveis elevados de gonadotrofina coriônica foram associados ao desenvolvimento de NTG em MHCFC / Objective: To determine the clinical characteristics and outcomes of multiple pregnancies with complete mole and coexisting normal fetus (CHMCF) in New England Trophoblastic Disease Center (NETDC) and Brazilian trophoblastic disease centers (BTDC). Methods: Retrospective non-concurrent cohorts comprised of CHMCF from NETDC (1966-2015) and four BTDC (1990-2015). Comparisons were made regarding: geographical location from 1990 to 2015 (NETDC vs BTDC), two different periods of time in NETDC (1966-1989 vs 1990-2015) and patients who developed gestational trophoblastic neoplasia (GTN) with the ones that spontaneously regressed. Results: From a total of 12,455 cases of gestational trophoblastic disease seen at the referral centers, 72 CHMCF were identified. Clinical characteristics and outcomes were similar between BTDC (n=46) and NETDC (n=13) from 1990 to 2015, apart from a much higher frequency of potentially life-threatening conditions in Brazil (p=0.046). There were no significant changes in the clinical presentation or outcomes in two different time periods in NETDC (13 cases in 1966-1989 vs 13 cases in 1990-2015). Ten pregnancies were electively terminated (14% of 70 cases with available obstetric outcome) and 36 resulted in viable live infants (60% of 60 pregnancies that were expectantly managed). The rate of GTN was 46% (31 out of 68 cases with available information on GTN development); the cases that progressed to GTN presented with higher chorionic gonadotropin levels (250.000 mIU/mL vs 120.000 mIU/mL; p=0.026), lower gestational age at the end of pregnancy (17 weeks vs 28,5 weeks; p < 0,001), lower fetal viability (27% vs 69%; p < 0,001), higher rate of spontaneous abortions (35% vs 9%; p=0.020) and higher frequency of termination of pregnancy due to medical complications (26% vs 0%; p=0.003) when compared to those with spontaneous remission. However, elective termination of pregnancy was not associated with GTN development. Conclusions: The main regional difference in CHMCF was related to a higher rate of potentially life-threatening conditions in Brazil. Most of the women with CHMCF who were managed expectantly delivered a viable fetus. CHMCF exhibited a high GTN rate. Elective termination of pregnancy did not influence the risk for GTN; however the need for termination due to severe medical complications, spontaneous abortions, lower gestational age at the end of pregnancy, lower fetal viability and higher hCG levels were associated with GTN progression in CHMCF Doença trofoblástica gestacional Gravidez de gêmeos Gravidez múltipla Mola hidatiforme Near miss Neoplasia trofoblástica gestacional Gestational trophoblastic disease Hydatidiform mole Near miss healthcare Pregnancy twin Pregnancy multiple Trophoblastic neoplasms
14	Recherche de biomarqueurs prédictifs de l’évolution et de la réponse au traitement dans les maladies trophoblastiques gestationnelles / Identification of predictive biomarkers for the evolution and treatment response of gestational trophoblastic diseases Bolze, Pierre-Adrien 26 June 2019 (has links) Les môles hydatiformes sont une prolifération placentaire prétumorale pouvant évolueren tumeur alors traitée par chimiothérapie. Afin de réduire la mortalité et d’optimiser laprise en charge thérapeutique, l’objectif de cette thèse est d’identifier les gènespermettant de prédire la transformation en tumeur post môlaire et la chimiorésistance.Concernant la prédiction de la transformation, l’analyse de l’expression de gènescandidatssur tissu molaire décrit la relocalisation apicale de la Syncytine-1 en cas detransformation maligne, sans modification de transcription de ses récepteurs ni de deuxautres enveloppes rétrovirales placentaires. L’analyse sans à priori du transcriptome par3 méthodes différentes n’a pas permis d’identifier de gène différentiellement expriméselon la transformation. Cela suggère que la variabilité interindividuelle et les diverscritères utilisés pour le diagnostic de tumeur nuisent à l’identification de biomarqueursrobustes.Concernant la prédiction de la chimiorésistance, une approche transcriptomique largespectre sur tissu tumoral de choriocarcinome identifie une réduction de transcriptiond’HLA-G en cas de monochimiorésistance, confirmée au niveau protéique par immunohistochimie. L’analyse en réseaux de l’ensemble des gènes différentiellementexprimés suggère que la monochimiorésistance est associée à une altération de ladifférenciation des lymphocytes T alors que la polychimiorésistance est associée à unealtération de la prolifération des cellules sanguines.In fine, l’objectivation de l’expression trophoblastique du point de contrôle PD-L1 aconduit à évaluer l’efficacité d’un anti PD-L1 chez les patientes chimiorésistantes. Lesrésultats encourageants de cet essai et la possibilité de stratifier les patientes à l’aidedes marqueurs HLA-G et Syncytine-1 incitent à évaluer la place de l’anti PD-L1 associéà une monochimiothérapie en première ligne de traitement des tumeurstrophoblastiques. / Hydatidiform moles are a pretumoral placental proliferation which can turn into a tumorrequiring chemotherapy. In order to reduce mortality and propose an optimal therapeuticmanagement, the aim of this thesis is to identify genes which are predictive of postmolartumor transformation and chemoresistance.Concerning the prediction of transformation, the expression analysis of candidate-geneson molar tissue shows a relocalization of Syncytin-1 at the syncytiotrophoblast apicalborder in moles followed by malignant transformation, without modification oftranscription of its receptors and two other retroviral placental envelopes. A wholetranscriptomeapproach using 3 different microarrays-based methods did not identify anydifferentially expressed gene according to the post molar evolution. This may reflect thatinter-individual variability and the different criteria used for tumor diagnosis impede theidentification of robust biomarkers.Concerning the prediction of chemoresistance, a broad-spectrum transcriptomicapproach on choriocarcinoma tumor tissue identifies a down regulation of HLA-G in case of monochemoresistance, confirmed at the protein level by immunohistochemistry.Pathway analysis of the differentially expressed genes suggests thatmonochemoresistance is associated with impaired T-cell differentiation, whereaspolychemoresistance is associated with impaired proliferation of blood cells.Ultimately, the evidence of trophoblastic ubiquitous expression of the PD-L1 immunecheckpoint led us to the evaluation of the efficacy of PD-L1 blockade in chemoresistantpatients. The encouraging results of this trial and the possibility of stratifying patientswith HLA-G and Syncytin-1 markers encourages the assessment of PD-L1 blockadecombined with monochemotherapy as a first line treatment for trophoblastic tumors. Biomarqueur Immunotolérance Chimiothérapie Môle hydatiforme Choriocarcinome Rétrovirus endogènes humains Immunothérapie Transformation tumorale Tumeur trophoblastique Biomarker Immunotolerance Chemotherapy Hydatidiform mole Choriocarcinoma Human endogenous retriovirus Immunotherapy Malignant transformation Trophoblastic tumor
15	A Novel Approach to Identify Candidate Imprinted Genes in Humans Shapiro, Jonathan 21 March 2012 (has links) Many imprinted genes are necessary for normal human development. Approximately 70 imprinted genes have been identified in humans. I developed a novel approach to identify candidate imprinted genes in humans using the premise that imprinted genes are often associated with nearby parent-of-origin-specific DNA differentially methylated regions (DMRs). I identified parent-of-origin-specific DMRs using sodium bisulfite-based DNA (CpG) methylation profiling of uniparental tissues, mature cystic ovarian teratoma (MCT) and androgenetic complete hydatidiform mole (AnCHM), and biparental tissues, blood and placenta. In support of this approach, the CpG methylation profiling led to the identification of parent-of-origin-specific differentially methylated CpG sites (DMCpGs) in known parent-of-origin-specific DMRs. I found new DMRs for known imprinted genes NAP1L5 and ZNF597. Most importantly, I discovered many new DMCpGs, which were associated with nearby genes, i.e., candidate imprinted genes. Allelic expression analyses of one candidate imprinted gene, AXL, suggested polymorphic imprinting of AXL in human blood. Allele Allele-specific DNA Methylation Allele-specific Gene Expression Allele-specific Expression Allele-specific Methylation AnCHM Androgenetic Androgenetic Mole Mole Complete Mole Hydatidiform Mole Complete Hydatidiform Mole Androgenetic Hydatidiform Mole Androgenetic Complete Hydatidiform Mole Biparental Tissue Bisulfite Bisulphite Blood Blood DNA Computational Biology DNA Methylation DNA Methylation Profiling Epigenetic Epi-genetic Epigenomic Epi-genomic Expression Expression Regulation Gene Expression Gene Expression Regulation Genetic Genetic Imprint Genetic Imprinting Genomic Genomic DNA Genomic Imprint Genomic Imprinting Human Imprint Imprinting Teratoma Ovarian Teratoma Cystic Teratoma Mature Teratoma Mature Cystic Teratoma Mature Ovarian Teratoma Cystic Ovarian Teratoma Mature Cystic Ovarian Teratoma MCT Methylation Cytosine Methylation Microarray Neoplasm Ovarian Neoplasm Placenta Profiling Promoter Promoter Region Sodium Bisulfite Sodium Bisulphite Uniparental Tissue WB WBC Imprinted Gene Polymorphic Imprinting Parent-of-origin Parent-of-origin-specific Methylation Parent-of-origin-specific Expression 0369 0307
16	A Novel Approach to Identify Candidate Imprinted Genes in Humans Shapiro, Jonathan 21 March 2012 (has links) Many imprinted genes are necessary for normal human development. Approximately 70 imprinted genes have been identified in humans. I developed a novel approach to identify candidate imprinted genes in humans using the premise that imprinted genes are often associated with nearby parent-of-origin-specific DNA differentially methylated regions (DMRs). I identified parent-of-origin-specific DMRs using sodium bisulfite-based DNA (CpG) methylation profiling of uniparental tissues, mature cystic ovarian teratoma (MCT) and androgenetic complete hydatidiform mole (AnCHM), and biparental tissues, blood and placenta. In support of this approach, the CpG methylation profiling led to the identification of parent-of-origin-specific differentially methylated CpG sites (DMCpGs) in known parent-of-origin-specific DMRs. I found new DMRs for known imprinted genes NAP1L5 and ZNF597. Most importantly, I discovered many new DMCpGs, which were associated with nearby genes, i.e., candidate imprinted genes. Allelic expression analyses of one candidate imprinted gene, AXL, suggested polymorphic imprinting of AXL in human blood. Allele Allele-specific DNA Methylation Allele-specific Gene Expression Allele-specific Expression Allele-specific Methylation AnCHM Androgenetic Androgenetic Mole Mole Complete Mole Hydatidiform Mole Complete Hydatidiform Mole Androgenetic Hydatidiform Mole Androgenetic Complete Hydatidiform Mole Biparental Tissue Bisulfite Bisulphite Blood Blood DNA Computational Biology DNA Methylation DNA Methylation Profiling Epigenetic Epi-genetic Epigenomic Epi-genomic Expression Expression Regulation Gene Expression Gene Expression Regulation Genetic Genetic Imprint Genetic Imprinting Genomic Genomic DNA Genomic Imprint Genomic Imprinting Human Imprint Imprinting Teratoma Ovarian Teratoma Cystic Teratoma Mature Teratoma Mature Cystic Teratoma Mature Ovarian Teratoma Cystic Ovarian Teratoma Mature Cystic Ovarian Teratoma MCT Methylation Cytosine Methylation Microarray Neoplasm Ovarian Neoplasm Placenta Profiling Promoter Promoter Region Sodium Bisulfite Sodium Bisulphite Uniparental Tissue WB WBC Imprinted Gene Polymorphic Imprinting Parent-of-origin Parent-of-origin-specific Methylation Parent-of-origin-specific Expression 0369 0307

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