LINDA FERREIRA MAXIMIANO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
SCCIRGR-62, Hospital Universitário
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
SCCIRGR-62, Hospital Universitário
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- Cachexia causes time-dependent activation of the inflammasome in the liver(2023) NEVES, Rodrigo Xavier das; YAMASHITA, Alex S.; RICCARDI, Daniela M. R.; KOHN-GAONE, Julia; CAMARGO, Rodolfo G.; NETO, Nelson I.; CAETANO, Daniela; GOMES, Silvio P.; SANTOS, Felipe H.; LIMA, Joanna D. C. C.; JR, Miguel L. Batista; ROSA-NETO, Jose Cesar; ALCANTARA, Paulo Sergio Martins De; MAXIMIANO, Linda F.; OTOCH, Jose P.; TRINCHIERI, Giorgio; TIRNITZ-PARKER, Janina E. E.; SEELAENDER, MariliaBackgroundCachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient. MethodsColon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 x 10(7) cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline-controls [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. ResultsIn rodent cachexia, we found progressively higher numbers of CD68(+) myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukin-1 beta (IL-1 beta) form (P < 0.05 for both circulating and hepatic content). ConclusionsThe results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1 beta.
- Systemic Inflammation in Cachexia - Is Tumor Cytokine Expression Profile the Culprit?(2015) MATOS-NETO, Emidio M. de; LIMA, Joanna D. C. C.; PEREIRA, Welbert O. de; FIGUEREDO, Raquel G.; RICCARDI, Daniela M. dos R.; RADLOFF, Katrin; NEVES, Rodrigo X. das; CAMARGO, Rodolfo G.; MAXIMIANO, Linda F.; TOKESHI, Flavio; OTOCH, Jose P.; GOLDSZMID, Romina; CAMARA, Niels O. S.; TRINCHIERI, Giorgio; ALCANTARA, Paulo S. M. de; SEELAENDER, MariliaCachexia affects about 80% of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions among tumor, immune cells, and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix (R) system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4, and IL-I beta expression was higher in the adipose tissue and tumor tissue in the cachectic group. In both tissues, chemotactic factors were positively correlated with IL-1 beta. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.
- Plasma Lipid Profile and Systemic Inflammation in Patients With Cancer Cachexia(2020) RICCARDI, Daniela Mendes dos Reis; NEVES, Rodrigo Xavier das; MATOS-NETO, Emidio Marques de; CAMARGO, Rodolfo Gonzalez; LIMA, Joanna Darck Carola Correia; RADLOFF, Katrin; ALVES, Michele Joana; COSTA, Raquel Galvao Figueredo; TOKESHI, Flavio; OTOCH, Jose Pinhata; MAXIMIANO, Linda Ferreira; ALCANTARA, Paulo Sergio Martins de; COLQUHOUN, Alison; LAVIANO, Alessandro; SEELAENDER, MariliaCancer cachexia affects about 80% of advanced cancer patients, it is linked to poor prognosis and to date, there is no efficient treatment or cure. The syndrome leads to progressive involuntary loss of muscle and fat mass induced by systemic inflammatory processes. The role of the white adipose tissue (WAT) in the onset and manifestation of cancer cachexia gained importance during the last decade. WAT wasting is not only characterized by increased lipolysis and release of free fatty acids (FFA), but in addition, owing to its high capacity to produce a variety of inflammatory factors. The aim of this study was to characterize plasma lipid profile of cachectic patients and to correlate the FA composition with circulating inflammatory markers; finally, we sought to establish whether the fatty acids released by adipocytes trigger and/or contribute to local and systemic inflammation in cachexia. The study selected 65 patients further divided into 3 groups: control (N); weight stable cancer (WSC); and cachectic cancer (CC). The plasma FA profile was significantly different among the groups and was positively correlated with pro-inflammatory cytokines expression in the CC patients. Therefore, we propose that saturated to unsaturated FFA ratio may serve as a means of detecting cachexia.
- Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa(2019) COSTA, Raquel G. F.; CARO, Paula L.; MATOS-NETO, Emidio M. de; LIMA, Joanna D. C. C.; RADLOFF, Katrin; ALVES, Michele J.; CAMARGO, Rodolfo G.; PESSOA, Ana Flavia M.; SIMOES, Estefania; GAMA, Patricia; CARA, Denise C.; SILVA, Aloisio S. F. da; PEREIRA, Welbert O.; MAXIMIANO, Linda F.; ALCANTARA, Paulo S. M. de; OTOCH, Jose P.; TRINCHIERI, Giorgio; LAVIANO, Alessandro; MUSCARITOLI, Maurizio; SEELAENDER, MariliaBackground Cachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterized by severe involuntary body weight loss, disrupted metabolism, inflammation, anorexia, fatigue, and diminished quality of life. This syndrome affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation has been recently proposed to underline most of cachexia-related symptoms. Nevertheless, the exact mechanisms leading to the initiation of systemic inflammation have not yet been unveiled, as patients bearing the same tumour and disease stage may or may not present cachexia. We hypothesize a role for gut barrier disruption, which may elicit persistent immune activation in the host. To address this hypothesis, we analysed the healthy colon tissue, adjacent to the tumour. Methods Blood and rectosigmoid colon samples (20 cm distal to tumour margin) obtained during surgery, from cachectic (CC = 25) or weight stable (WSC = 20) colon cancer patients, who signed the informed consent form, were submitted to morphological (light microscopy), immunological (immunohistochemistry and flow cytometry), and molecular (quantification of inflammatory factors by Luminex (R) xMAP) analyses. Results There was no statistical difference in gender and age between groups. The content of plasma interleukin 6 (IL-6) and IL-8 was augmented in cachectic patients relative to those with stable weight (P = 0.047 and P = 0.009, respectively). The number of lymphocytic aggregates/field in the gut mucosa was higher in CC than in WSC (P = 0.019), in addition to those of the lamina propria (LP) eosinophils (P < 0.001) and fibroblasts (P < 0.001). The area occupied by goblet cells in the colon mucosa was decreased in CC (P = 0.016). The M1M2 macrophages percentage was increased in the colon of CC, in relation to WSC (P = 0.042). Protein expression of IL-7, IL-13, and transforming growth factor beta 3 in the colon was significantly increased in CC, compared with WSC (P = 0.02, P = 0.048, and P = 0.048, respectively), and a trend towards a higher content of granulocyte-colony stimulating factor in CC was also observed (P = 0.061). The results suggest an increased recruitment of immune cells to the colonic mucosa in CC, as compared with WSC, in a fashion that resembles repair response following injury, with higher tissue content of IL-13 and transforming growth factor beta 3. Conclusions The changes in the intestinal mucosa cellularity, along with modified cytokine expression in cachexia, indicate that gut barrier alterations are associated with the syndrome.