Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.

Thesis (Ph.D.)--Murdoch University, 2004. / Thesis submitted to the Division of Health Sciences. Bibliography: leaves 276-318.

Thesis (M.S. )--University of Tennessee Health Science Center, 2006. / Title from title page screen (viewed on October 17, 2008). Research advisor: Edward Harris, Ph.D. Document formatted into pages (xxvii, 301 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 133-153).

Made available in DSpace on 2014-06-11T19:23:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-04-01Bitstream added on 2014-06-13T19:29:04Z : No. of bitstreams: 1 duarte_pd_me_botfm.pdf: 611993 bytes, checksum: ccf0323dc58e760455c77b8af2abcf44 (MD5) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / Fundação Amaral Carvalho / Leucemia Linfóide Crônica (LLC) é uma neoplasia maligna de linfócitos B maduros com aspecto monomórfico, que se acumulam em tecidos linfóides secundários, medula óssea e sangue periférico. O diagnóstico é realizado com base em achados clínico-morfológicos e imunofenotípicos. Os pacientes com LLC são estratificados conforme o estadiamento clínico para definição de terapêutica; atualmente a descoberta de marcadores prognósticos, como ZAP-70, trouxe novas perspectivas ao tratamento, principalmente no estádio precoce. Os objetivos deste estudo foram: avaliar a eficácia da pesquisa da ZAP-70 em biópsia de medula óssea (BMO) e em inclusão do coágulo, utilizando-se a técnica de imuno-histoquímica; avaliar possíveis correlações deste marcador na BMO com evolução clínica e risco de progressão; correlacionar a imuno-expressão da ZAP- 70 com o arcabouço reticulinico das BMO; avaliar se este arcabouço possui correlação com o prognostico da doença e, por fim, traçar um perfil epidemiológico dos pacientes com LLC atendidos no Hospital das Clinicas da Faculdade de Medicina de Botucatu (FMB). Foram selecionados 153 pacientes com LLC, atendidos no ambulatório do Serviço de Hematologia da FMB-UNESP, de 1980 a 2008, e 9 pacientes assistidos no Serviço de Onco-Hematologia do Hospital Amaral Carvalho-Jaú, no período de 2000 a 2008, com o mesmo diagnóstico, perfazendo 162 casos. Destes, 79 possuíam prontuários que foram revisados, bem como dados morfológicos da BMO e AMO. Foi realizada a pesquisa da ZAP- 70 pela técnica de imuno-histoquímica nas amostras parafinadas de BMO e inclusão do coágulo. Observou-se que 55,7% dos pacientes eram do sexo masculino; 86,1% de etnia branca; a mediana de idade foi 65 anos; relação homem:mulher de 1,2:1. 40,5% dos pacientes tiveram diagnóstico por achado incidental e 73,4%, já com adenopatia secundária à admissão. 17,2%... / Chronic lymphocytic leukemia (CLL) is a malignant neoplasm consisting of mature monomorphic B lymphocytes that accumulate in secondary lymphoid tissues, bone marrow and peripheral blood. Diagnosis is based on clinical, morphological and immunophenotypic findings. CLL patients are categorized according to clinical aspects for treatment management and currently, certain tools, such as prognostic marker ZAP- 70, have determined new treatment perspectives, especially for patients in early stages. The study aimed to evaluate the efficiency of ZAP-70 investigation in bone marrow biopsies (BMBs) and inclusion coagulate using immunohistochemistry; identify possible correlations of this marker in clinical evolution and risk of progression; correlate the immunoexpression of ZAP-70 with BMB reticulin network; evaluate whether this network correlates with disease prognosis and; outline an epidemiological profile of patients with CLL attended in the Clinics Hospital of Botucatu Faculty of Medicine (FMB). The sample consisted of 153 CLL patients attended at hematology outpatient clinic of the FMB-UNESP, from 1980 to 2008, and 9 CLL patients attended at the oncohematology service of the Amaral Carvalho Hospital, Jaú, from 2000 to 2008, totaling 162 cases. In 79 cases, medical records including BMB and bone marrow aspirate (BMA) morphological data were reviewed. Immunohistochemistry for ZAP-70 was conducted on paraffinated samples of BMB and inclusion coagulate. Observation revealed that: 55.7% were male, 86.1% white, with a median age of 65 years-old; 40.5% of cases were diagnosed by incidental findings in routine blood smears; 73.4% were diagnosed with peripheral adenomegaly on admission. 17.2% were diagnosed in the early stages and 15% of cases showed prolonged remission. BMB and BMA morphology revealed that 94.8% of patients presented increased cellularity... (Complete abstract click electronic access below)

Les métastases hépatiques compliquent l'évolution de 50% des cancers colorectaux (CCR). Plus de la moitié des patients présentent une récidive à distance avec métastases occultes pour lesquelles une chirurgie peut être réalisée dans moins de 20% des cas. L'ablation par radiofréquence (RFA) induit une réponse lymphocytaire T qui n'est pas évaluée après une intervention chirurgicale seule. L'immunothérapie combinée à la RFA pourrait potentialiser cet effet conduisant à une réponse tumorale à distance. Nous proposons une approche qui combine la RFA avec hydrogel thermoreversible libérant des agents immunomodulateurs (GMCSF et BCG) sur le site du traitementPremièrement, nous nous sommes intéressés à la sélection et à la caractérisation de la formulation optimale d’hydrogel par des techniques physicochimiques. Les propriétés de l'hydrogel ont été étudiées par rhéologie et des tests de muco-adhésion ont été mis en place. Le temps de résidence de l'hydrogel et de la protéine dans la zone tumorale a été démontré par imagerie optique. De plus, la cinétique de libération et l'intégrité du GMCSF encapsulé ont été déterminées. Ensuite, nous avons démontré l’efficacité de l’association de la RFA avec le dépôt local de l’hydrogel immunomodulatuer sur un modèle murin de cancer colorectal. En effet, nous avons observé une survie améliorée des animaux et régression complète des tumeurs distantes chez les animaux traités par la combinaison complète. Cette réponse est caractérisée par un niveau élevé de sécrétion de cytokines pro-inflammatoires par les cellules T CD4 et TCD8 et une augmentation de l’infiltrat lymphocytaire dans les tumeurs. Ceci a permis d'envisager une association avec l'immunothérapie anti-PD1 dans le traitement de macrométastases échappant au traitement combiné RFA avec l’hydrogel immunomodulateur. En effet, l’immunothérapie dans le traitement du cancer colorectal métastatique présente une efficacité limitée chez les patients. Notre travail propose a démontré que l’efficacité de l’immunomodulation locale dans l’amélioration des réponses immunitaires dans le cancer colorectal. Ces résultats permettent de reconsidérer l’utilisation de l’immunothérapie chez les patients atteints de CCR métastatique non MSI. / Liver metastases complicate the progression of 50% of colorectal cancers (CRC). More than half of the patients have recurrent remissions with occult metastases for which surgery can be performed in less than 20% of cases. Radiofrequency ablation (RFA) induces a T lymphocyte response that is not observed after surgery alone. Combined immunotherapy with RFA may potentiate this effect leading to a distant tumor response. We propose an approach that combines RFA with thermoreversible hydrogel releasing immunomodulatory agents (GMCSF and BCG) at the treatment site.First, we focused on the selection and characterization of the optimal hydrogel formulation by physicochemical techniques. The properties of the hydrogel were studied by rheology and mucoadhesion tests were set up. The residence time of the hydrogel and the protein in the tumor zone was demonstrated by optical imaging. In addition, the release kinetics and integrity of the encapsulated GMCSF were determined. Then, we demonstrated the effectiveness of the combination of RFA with the local deposition of the immunomodulatory hydrogel on a mouse model of colorectal cancer. Indeed, we observed improved survival of animals and complete regression of distant tumors the complete treatment group. This response is characterized by a high level of pro-inflammatory cytokine secreted by CD4 and TCD8 T cells and an increase Lymphocytes infiltrating tumors. The immune escape of large lesions was reversed by association with anti-PD1 immunotherapy Indeed, immunotherapy in the treatment of metastatic colorectal cancer has limited efficacy in patients. Our work has demonstrated the effectiveness of local immunomodulation in improving immune responses in colorectal cancer. These results make it possible to reconsider the use of immunotherapy in patients with non-MSI metastatic CRC.

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Background and study aims: It has been suggested that smoking may be associated with microscopic colitis (MC) in some studies; however, there are conflicting results in the current literature with many of these studies having significant limitations. Our study aims to offer a meta-analysis evaluating the association between MC, including both its subtypes, and smoking. Patients and methods: A systemic review was conducted in PUBMED, Embase, PubMed Central, and ScienceDirect databases from inception through December 2019. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird and a pooled odds ratio (OR) was calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques. Results: Eight observation studies with a total of 1461 patients with MC were included in this study, 383 of whom were active smokers (26.2%). Current smoking was significantly associated with MC (OR 3.58, 95% CI, 2.51–5.11), lymphocytic colitis (LC) (OR 3.64, 95% CI, 2.46–5.38), and collagenous colitis (CC) (OR 4.43, 95% CI, 2.68–7.32). Gender-specific subgroup analysis showed a significant association with smoking was found for CC in men (OR 4.53, 95% CI, 1.59–12.85), CC in women (OR 3.27, 95% CI, 2.35–4.54), LC in women (OR 2.27, 95% CI, 1.27–4.06) and MC in women (OR 2.93, 95% CI, 2.09–4.10). We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test. Conclusion: Our meta-analysis found a statistically significant association between smoking and both subtypes of MC.

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