PAULO SERGIO MARTINS DE ALCANTARA
Projetos de Pesquisa
Unidades Organizacionais
DVCLCIR-62, Hospital Universitário
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- White adipose tissue IFN-gamma expression and signalling along the progression of rodent cancer cachexia(2017) YAMASHITA, Alex Shimura; NEVES, Rodrigo Xavier das; ROSA-NETO, Jose Cesar; LIRA, Fabio dos Santos; BATISTA JR., Miguel Luis; ALCANTARA, Paulo Sergio; OTOCH, Jose Pinhata; SEELAENDER, MariliaCachexia is associated with increased morbidity and mortality in cancer. The White adipose tissue (WAT) synthesizes and releases several pro-inflammatory cytokines that play a role in cancer cachexia-related systemic inflammation. IFN-gamma is a pleiotropic cytokine that regulates several immune and metabolic functions. To assess whether IFN-gamma signalling in different WAT pads is modified along cancer-cachexia progression, we evaluated IFN-gamma receptors expression (IFNGR1 and IFNGR2) and IFN-gamma protein expression in a rodent model of cachexia (7, 10, and 14 days after tumour implantation). IFN-gamma protein expression was heterogeneously modulated in WAT, with increases in the mesenteric pad and decreased levels in the retroperitoneal depot along cachexia progression. Ifngr1 was up-regulated 7 days after tumour cell injection in mesenteric and epididymal WAT, but the retroperitoneal depot showed reduced Ifngr1 gene expression. Ifngr2 gene expression was increased 7 and 14 days after tumour inoculation in mesenteric WAT. The results provide evidence that changes in IFN-gamma expression and signalling may be perceived at stages preceding refractory cachexia, and therefore, might be employed as a means to assess the early stage of the syndrome.
- Adipose tissue fibrosis in human cancer cachexia: the role of TGF beta pathway(2017) ALVES, Michele Joana; FIGUEREDO, Raquel Galvao; AZEVEDO, Flavia Figueiredo; CAVALLARO, Diego Alexandre; PINTO NETO, Nelson Inacio; LIMA, Joanna Darck Carola; MATOS-NETO, Emidio; RADLOFF, Katrin; RICCARDI, Daniela Mendes; CAMARGO, Rodolfo Gonzalez; ALCANTARA, Paulo Sergio Martins De; OTOCH, Jose Pinhata; BATISTA JUNIOR, Miguel Luiz; SEELAENDER, MariliaBackground: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGF beta) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGF beta in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGF beta pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. Methods: After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGF beta isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (aSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. Results: There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of aSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGF beta 1 and TGF beta 3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue. Conclusions: Cancer cachexia promotes the development of AT fibrosis, in association with altered TGF beta signaling, compromising AT organization and function.
- Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer(2017) SILVERIO, Renata; LIRA, Fabio S.; OYAMA, Lila M.; NASCIMENTO, Claudia M. Oller do; OTOCH, Jose P.; ALCANTARA, Paulo S. M.; BATISTA JR., Miguel L.; SEELAENDER, MariliaBackground: Cancer cachexia is a multifactorial metabolic syndrome characterized by marked loss of adipose tissue and skeletal muscle. Fat loss from adipose tissue in cancer cachexia is partly the result of increased lipolysis. Despite the growing amount of studies focused on elucidating the mechanisms through which lipolysis-related proteins regulate the lipolytic process, there are scarce data concerning that profile in the adipose tissue of cancer cachectic patients. Considering its fundamental importance, it was our main purpose to characterize the expression of the lipolysis-related proteins in the white adipose tissue of cachectic cancer patients. Methods: Patients from the University Hospital were divided into three groups: control, cancer cachexia (CC), and weight-stable cancer patients (WSC). To gain greater insight into adipose tissue wasting during cancer cachexia progression, we have also analyzed an experimental model of cachexia (Walker 256 carcinosarcoma). Animals were divided into: control, intermediate cachexia (IC) and terminal cachexia (TC). Subcutaneous white adipose tissue of patients and epidydimal white adipose tissue of animals were investigated regarding molecular aspects by determining the protein content and gene expression of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), perilipin 1, leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha). Results: We found augmented lipolysis in CC associated with increased HSL expression, as well as upregulation of ATGL expression and reduction in perilipin 1 content. In IC, there was an imbalance in the secretion of pro-and anti-inflammatory factors. The alterations at the end-stage of cachexia were even more profound, and there was a reduction in the expression of almost all proteins analyzed in the animals. Conclusions: Our findings show that cachexia induces important morphological, molecular, and humoral alterations in the white adipose tissue, which are specific to the stage of the syndrome.