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Doctoral Thesis
DOI
10.11606/T.42.2016.tde-10112016-153540
Document
Author
Full name
Michele Joana Alves
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Seelaender, Marilia Cerqueira Leite (President)
Chammas, Roger
Colquhoun, Alison
Puschel, Gerhard Paul
Werneck, Claudio Chrysostomo
Title in Portuguese
Caquexia associada ao câncer: a contribuição da via de sinalização do TGFβ na fibrose do tecido adiposo.
Keywords in Portuguese
Caquexia associada ao câncer
Fibrose
Matriz extracelular
Tecido adiposo
TGFβ
Abstract in Portuguese
O objetivo do estudo foi investigar o remodelamento tecidual e fatores modulados pela via do TGFβ no tecido adiposo subcutâneo na vigência da caquexia associada ao câncer gastrointestinal. O estudo incluiu 59 pacientes divididos em três grupos: Controle, Câncer de peso estável (WSC) e Câncer e Caquexia (CC). Foram observadas alterações morfológicas exclusivas ao tecido adiposo do grupo CC. Houve o aumento na deposição de colágeno, glicoproteínas associadas, e fibras do sistema elásticas. A imunohistoquímica revelou alterações no conteúdo dos colágenos do tipo I, III e VI, e da fibronectina no grupo CC em relação ao grupo Controle e WSC. A presença de miofibroblastos no grupo CC foi confirmada pela imunomarcação para αSMA, e o aumento de 20 vezes do gene FSP1 no tecido adiposo, em associação com expressiva marcação de vimentina em fibroblastos isolados. As concentrações do TGFβ3 estavam aumentadas no tecido adiposo, e TGFβ1 e TGFβ3 nos adipócitos, dos pacientes caquéticos. A imunolocalização revelou maior intensidade para SMAD3 e SMAD4 no grupo CC. Em conclusão, na caquexia associada ao câncer, a via do TGFβ contribui para o comprometimento da biologia do tecido adiposo e o desenvolvimento da fibrose.
Title in English
Cancer cachexia: TGFβ pathway contribution in adipose tissue fibrosis.
Keywords in English
Adipose tissue
Cancer cachexia
Extracellular matrix
Fibrosis
TGFβ
Abstract in English
Aim of the study was to investigate tissue remodelling and factors modulated by TGFβ pathway in the subcutaneous adipose tissue in gastrointestinal cancer cachexia. The study included 59 patients enrolled into three groups: Control, Weight-stable Cancer (WSC) and Cancer Cachexia (CC). Morphological alterations (HE) were observed in adipose tissue from CC group solely, with reduction in the content of fat cells (area, diameter and circumference). Markedly stain to collagens type I, III, IV and fibronectin by immunohistochemistry revealed changes in the CC group as compared to the control and WSC group. Presence of myofibroblasts in CC group was observed by immunostaining for αSMA, and 20-fold increase of the FSP1 gene in adipose tissue. In association, was reported higher expression for vimentin in isolated fibroblasts. TGFβ3 concentrations were enhanced in adipose tissue, and TGFβ1 and TGFβ3 in adipocytes of cachectic patients in relation to control group. Immunolocalization revealed greater intensity for SMAD3 and SMAD4 in the CC group. Thus, during cancer cachexia the TGFβ pathway contributes to disruption of adipose tissue biology and fibrosis development.
 
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Release Date
2018-11-10
Publishing Date
2016-11-10
 
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