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
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia(2021) JESUS, Joyce de Cassia Rosa de; MURARI, Ariene Soares de Pinho; RADLOFF, Katrin; MORAES, Ruan Carlos Macedo de; FIGUEREDO, Raquel Galvao; PESSOA, Ana Flavia Marcal; ROSA-NETO, Jose Cesar; MATOS-NETO, Emidio Marques; ALCANTARA, Paulo S. M.; TOKESHI, Flavio; MAXIMIANO, Linda Ferreira; BIN, Fang Chia; FORMIGA, Fernanda Bellotti; OTOCH, Jose P.; SEELAENDER, MariliaBackground Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1 beta and IL-18. Aim based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-kappa B. Results For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-kappa B p50, NF-kappa B p65, IL-1 beta. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1 beta and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants. Conclusions The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.
- The learning curve of bilateral laparoscopic varicocelectomy: a prospective study(2023) BELKOVSKY, MIKHAEL; PASSEROTTI, CARLO CAMARGO; MAXIMIANO, LINDA FERREIRA; OTOCH, JOSÉ PINHATA; CRUZ, JOSE ARNALDO SHIOMI DAABSTRACT Varicocele occurs in 15% of general male population and in 35% of infertile men. Since 1992, surgical correction with laparoscopic varicocelectomy is the gold standard for treatment of symptomatic patients or patients with abnormal seminal analysis. The learning curve for this frequently performed procedure has not yet been described. In the present study, we investigated the learning curve of a single urologist in training performing his first 21 laparoscopic varicocelectomies using qualitative and quantitative tools to evaluate his performance during the process. Our results show that 14 bilateral laparoscopic varicocelectomies are enough to achieve the plateau of the learning curve.
- 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.
- The learning curve for retrograde intrarenal surgery: A prospective analysis(2022) SILVA, THIAGO HENRIQUE CAETANO DA; PASSEROTTI, CARLO CAMARGO; PONTES JÚNIOR, JOSÉ; MAXIMIANO, LINDA FERREIRA; OTOCH, JOSÉ PINHATA; CRUZ, JOSE ARNALDO SHIOMI DAABSTRACT Introduction: retrograde intrarenal surgery (CRIR) is an evolving tool. Its learning curve is not well established, despite the common use of flexible ureteroscopes today. Our aim is to estimate the number of procedures needed for one to perform RIRS consistently. Material and Methods: a urology resident had his first 80 RIRS for nephrolithiasis analyzed quantitatively and qualitatively. The procedures were divided into 4 groups containing 20 surgeries each (I to IV), according to their order, for comparison. Results: there was no difference in stone sizes between groups. All qualitative variables varied significantly between groups (p<0.001), except between III and IV. In the quantitative analysis, there was a difference between groups I and IV in time for double-J catheter placement (p=0.012). There was an increasing difference in sheath placement time (p<0.001) and in total operative time (p=0.004). The time fot stone treatment (p=0.011) was significant only between groups I, II and III. There was difference in total sheath time only between groups I and III (p=0.023). Stone free status did not change between groups. Discussion: the differences between the qualitative and quantitative variables show the relation between number of surgeries performed and proficiency in the procedure. Intergroup comparisons show sequential optimization of parameters. Conclusions: we found that 60 is a reasonable number of surgeries to be performed in order to reach the plateau of RIRSs learning curve.
- Bilateral inguinal transabdominal pre-peritoneal laparoscopic hernioplasty associated to bilateral laparoscopic varicocelectomy in the same intervention: a feasibility study(2023) BELKOVSKY, MIKHAEL; SARMENTO, EDGAR OLIVEIRA; NOVAES, LUIS FELIPE COUTO; PASSEROTTI, CARLO CAMARGO; PONTES JUNIOR, JOSÉ; MAXIMIANO, LINDA FERREIRA; OTOCH, JOSÉ PINHATA; DA-CRUZ, JOSE ARNALDO SHIOMIABSTRACT Introduction: Inguinal hernia and varicocele are common conditions in male population. Laparoscopy brings the opportunity to treat them simultaneously, through the same incision. However, there are different opinions about the risks for testicular perfusion of multiple procedures in the inguinal region. In this study, we assessed the feasibility of simultaneous laparoscopic procedures by studying clinical and surgical outcomes of patients undergoing bilateral inguinal hernioplasty using the transabdominal preperitoneal (TAPP) technique with and without concomitant bilateral laparoscopic varicocelectomy (VLB). Methods: a sample of 20 patients from the University Hospital of USP-SP with indirect inguinal hernia and varicocele with indication for surgical correction was selected. Patients were randomized into two groups, 10 undergoing TAPP (Group I) and 10 undergoing simultaneous TAPP and VLB (Group II). Data regarding total operative time, complications and postoperative pain was gathered and analyzed. Results: there was no statistical difference between groups regarding total operative time and postoperative pain. Only one complication (spermatic cord hematoma) was observed in Group I and no complications were observed in Group II. Conclusions: simultaneous TAPP and VLB in was shown to be effective and safe, which provides a basis for conducting studies on larger scales.
- Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients(2013) BATISTA JR., M. L.; OLIVAN, M.; ALCANTARA, P. S. M.; SANDOVAL, R.; PERES, S. B.; NEVES, R. X.; SILVERIO, R.; MAXIMIANO, L. F.; OTOCH, J. P.; SEELAENDER, M.Cachexia, a paraneoplastic syndrome markedly associated with worsened prognosis in cancer patients, provokes profound wasting of both lean and adipose mass in an association with a state of metabolic ""chaos"". The white adipose tissue responds to cachexia with marked local inflammation and may be thus a relevant contributor to systemic inflammation. To address this hypothesis we examined the correlation between tissue expression of adipokines and plasma concentration in cachectic and stable weight patients with or without cancer. Adiponectin and liver-derived CRP concentration were significantly higher in the cachectic groups when compared with stable weight patients (P < 0.01). The concentration of plasma IL-6 was higher (11.4-fold) in the cancer cachectic group when compared with weight-stable controls, and presented a significant correlation with the presence of cancer (P < 0.001). A marked increase (5-fold) in IL-6 as a result of the interaction between the presence of cachexia and the presence of tumour was observed in the subcutaneous tissue of the patients, yet not in the visceral depot. Plasma adiponectin levels were higher in cachectic cancer patients, compared with stable weight cancer patients individually matched by age, sex, and BMI, and the subcutaneous depot was found to be the main contributing tissue, rather than the visceral pad. Based on the results we concluded that the subcutaneous adipose tissue is associated with plasma changes that may function as markers of cachexia.
bookPart Atividades de Cirurgia Geral(2021) MITTELDORF, Cornelius; OTOCH, José Pinhata; ROCHA, Manoel de Souza; MAXIMIANO, Linda Ferreira- Learning curve of semi-rigid ureteroscopy for small calculi: how many cases are necessary?(2022) ILIAS, DANIEL; PASSEROTTI, CARLO CAMARGO; PONTES JUNIOR, JOSÉ; FAKHOURI, FELIPE; FARIA, SABRINA THALITA DOS REIS; MAXIMIANO, LINDA FERREIRA; OTOCH, JOSÉ PINHATA; DA-CRUZ, JOSE ARNALDO SHIOMIABSTRACT Introduction: semi-rigid ureteroscopy is the procedure of choice for the treatment of ureterolithiasis, but it requires a learning curve to be performed safely. Objective: To describe an estimate of the learning curve for performing semi-rigid ureterorenolithotripsy in patients with small-sized ureterolithiasis and to estimate the minimum number of procedures necessary to safely perform the surgical procedure. Methods: this is a prospective study evaluating the learning curve of a resident of urology in the first 60 semirigid ureteroscopies in patients with ureterolithiasis up to 1cm. The patients were divided into three groups: Group I one to twenty surgeries, Group II twenty one to forty surgeries and Group III forty one to sixty surgeries. The surgeries were recorded and analyzed by two urologists experienced in endourology. A qualitative analysis was performed based on a previously validated tool and a quantitative analysis. Results: all qualitative variables had significant variation between Groups I and II (p<0.001), and between Groups I and III (p<0.001). There was a difference in time to access the ureter, passage of a double J catheter and total operative time between Groups I and II (p<0.001) and Groups I and III (p<0.001). Conclusion: after 40 cases there seems to be little increase in both quantitative as well as qualitative evaluation in surgical performance for performing semi-rigid ureterolithotripsy safely in calculations up to 1cm.
- NF-kappa Bp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients(2015) CAMARGO, Rodolfo Gonzalez; RICCARDI, Daniela Mendes dos Reis; RIBEIRO, Henrique Quintas Teixeira; CARNEVALI JR., Luiz Carlos; MATOS-NETO, Emidio Marques de; ENJIU, Lucas; NEVES, Rodrigo Xavier; LIMA, Joanna Darck Carola Correia; FIGUEREDO, Raquel Galvao; ALCANTARA, Paulo Sergio Martins de; MAXIMIANO, Linda; OTOCH, Jose; BATISTA JR., Miguel Luiz; PUESCHEL, Gerhard; SEELAENDER, MariliaCancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-B). We have examined the gene expression of the subunits NF-Bp65 and NF-Bp50, as well as NF-Bp65 and NF-Bp50 binding, the gene expression of pro-inflammatory mediators under NF-B control (IL-1, IL-6, INF-, TNF-, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IB-). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-Bp65 and its target genes expression (TNF-, IL-1, MCP-1 and IB-) were significantly higher in cachectic cancer patients. Moreover, NF-Bp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-B pathway plays a role in the promotion of WAT inflammation during cachexia.