DAN LINETZKY WAITZBERG
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina - Líder
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study(2019) RAVACCI, Graziela Rosa; ISHIDA, Robson; TORRINHAS, Raquel Suzana; SALA, Priscila; MACHADO, Natasha Mendonca; FONSECA, Danielle Cristina; CANUTO, Gisele Andre Baptista; PINTO, Ernani; NASCIMENTO, Viviane; TAVARES, Marina Franco Maggi; SAKAI, Paulo; FAINTUCH, Joel; SANTO, Marco Aurelio; MOURA, Eduardo Guimaraes Hourneaux; ARTIGIANI NETO, Ricardo; LOGULLO, Angela Flavia; WAITZBERG, Dan LinetzkyWe evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (>= 4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.
- Metabolomic profiling of breast cancer and adjacent tissue(2017) SANTOS, J. R.; BRENTANNI, M. M.; TORTELLI, T.; DALE, I.; WAITZBERG, A.; WAITZBERG, D.; RAVACCI, G.
- Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass(2017) SALA, Priscila; BELARMINO, Giliane; TORRINHAS, Raquel S.; MACHADO, Natasha M.; FONSECA, Danielle C.; RAVACCI, Graziela R.; ISHIDA, Robson K.; GUARDA, Ismael F. M. S.; MOURA, Eduardo G. de; SAKAI, Paulo; SANTO, Marco A.; SILVA, Ismael D. C. G. da; PEREIRA, Claudia C. A.; LOGULLO, Angela F.; HEYMSFIELD, Steven; GIANNELLA-NETO, Daniel; WAITZBERG, Dan L.OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9 +/- 6.2 years; body mass index, 46.5 +/- 5.3 kg/m(2)) with adult-onset type 2 diabetes (fasting plasma glucose >= 126 mg/dl; hemoglobin A1c >= 6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P <= 0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P <= 0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.
- HER2-associated lipogenic phenotype as a potential therapeutical target in breast cancer patients(2017) RAVACCI, G. R.; SANTOS, J. R.; BRENTANI, M. M.; TORTELLI, T.; DALE, I.; LOGULLO, A. F.; WAITZBERG, D. L.
- Fecal bile acid profile after Roux-en-Y gastric bypass and its association with the remission of type 2 diabetes in obese women: A preliminary study(2019) CARDINELLI, Camila de Siqueira; TORRINHAS, Raquel Susana; SALA, Priscila; PUDENZI, Marcos Albieri; ANGOLINI, Celio Fernando F.; SILVA, Mariane Marques da; MACHADO, Natasha Mendonca; RAVACCI, Graziela; EBERLIN, Marcos N.; WAITZBERG, Dan L.Objective: To assess the influence of Roux-en-Y gastric by-pass (RYGB) on fecal bile acid (BA) profile and its relationship with postoperative remission of type 2 diabetes (T2D). Methods: Fecal samples were collected 3 and 12 months after RYGB from diabetic obese women who were responsive (n = 12) and non-responsive (n = 8) to postoperative remission of T2D. Fecal BA profile was accessed by liquid chromatography coupled to tandem mass spectrometry in a targeted approach. Results: Relative to pre-operative levels, a total of 10 fecal BA profiles decreased after RYGB (ANOVA, p <= 0.05) with significant fold-changes for glycochenodeoxycholic, glycocholic, taurocholic, and taurochenodeoxycholic acids at 3-months postoperatively, and for glycochenodeoxycholic, glycocholic and taurocholic acids at 12 months postoperatively (Benjamini-Hochberg, p < 0.05). Postoperative changes in fecal BA were different between responsive and non-responsive women, with a significant reduction in more sub-fractions of BA in responsive women than in non-responsive women, and a marked difference in the temporal behavior of cholic acid (CA) and chenodeoxycholic acid (CDCA), thus reflecting changes in CA/CDCA ratio, and tauroursodeoxycolic (TUDCA) levels between these responsiveness groups (ANOVA, p <= 0.05). Conclusion: RYGB induces a marked reduction in the concentration of fecal BA, which is heterogeneous according to T2D responsiveness.
- Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission(2020) SALA, Priscila; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; MACHADO, Natasha Mendonca; SINGER, Joelle; SINGER, Pierre; RAVACCI, Graziela Rosa; BELARMINO, Giliane; FERREIRA, Beatriz A. M.; MARQUES, Mariane; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; SUNAGA, Daniele Yumi; HEYMSFIELD, Steven B.; BEZERRA, Daniele Pereira dos Santos; CORREA-GIANNELLA, Maria Lucia; WAITZBERG, Dan LinetzkyObjectives: Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr Methods: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. Results: Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. Conclusions: RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.
- Complementarity of Subjective Global Assessment (SGA) and Nutritional Risk Screening 2002 (NRS 2002) for predicting poor clinical outcomes in hospitalized patients(2011) RASLAN, Mariana; GONZALEZ, Maria Cristina; TORRINHAS, Raquel Suzana M. M.; RAVACCI, Graziela Rosa; PEREIRA, Julio C. R.; WAITZBERG, Dan L.Background & aims: We evaluated the ability of Nutritional Risk Screening 2002 (NRS 2002) and Subjective Global Assessment (SGA) to predict malnutrition related to poor clinical outcomes. Methods: We assessed 705 patients at a public university hospital within 48 h of admission. Logistic regression and number needed to screen (NNS) were calculated to test the complementarity between the tools and their ability to predict very long length of hospital stay (VLLOS), complications, and death. Results: Of the patients screened, 27.9% were at nutritional risk (NRS+) and 38.9% were malnourished (SGA B or C). Compared to those patients not at nutritional risk, NRS+, SGA B or C patients were at increased risk for complications (p = 0.03, 0.02, and 0.003, respectively). NRS+ patients had an increased risk of death (p = 0.03), and SGA B and C patients had an increased likelihood of VLLOS (p = 0.008 and p < 0.0001, respectively). Patients who were both NRS+ and SGA C had lower estimates of NNS than patients who were NRS+ or SGA C only, though their confidence intervals did overlap. Conclusions: The concurrent application of SGA in NRS+ patients might enhance the ability to predict poor clinical outcomes in hospitalized patients in Brazil.
- Reduction of HER2-associated lipogenic phenotype by docosahexaenoic acid (DHA) induces apoptosis in breast tumor cells harboring HER2 overexpression(2015) RAVACCI, Graziela R.; BRENTANI, Maria M.; FESTUCCIA, William; TORTELLI, Tharcisio; WAITZBERG, Angela F.; WAITZBERG, Dan L.
- Phase angle obtained by bioelectrical impedance analysis independently predicts mortality in patients with cirrhosis(2017) BELARMINO, Giliane; GONZALEZ, Maria Cristina; TORRINHAS, Raquel S.; SALA, Priscila; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz Augusto Carneiro; PEREIRA, Rosa Maria R.; CAPARBO, Valeria F.; RAVACCI, Graziela R.; DAMIANI, Lucas; HEYMSFIELD, Steven B.; WAITZBERG, Dan L.AIM To evaluate the prognostic value of the phase angle (PA) obtained from bioelectrical impedance analysis (BIA) for mortality prediction in patients with cirrhosis. METHODS In total, 134 male cirrhotic patients prospectively completed clinical evaluations and nutritional assessment by BIA to obtain PAs during a 36-mo follow-up period. Mortality risk was analyzed by applying the PA cutoff point recently proposed as a malnutrition marker (PA <= 4.9 degrees) in Kaplan-Meier curves and multivariate Cox regression models. RESULTS The patients were divided into two groups according to the PA cutoff value (PA > 4.9 degrees, n = 73; PA <= 4.9 degrees, n = 61). Weight, height, and body mass index were similar in both groups, but patients with PAs > 4.9 degrees were younger and had higher mid-arm muscle circumference, albumin, and handgrip-strength values and lower severe ascites and encephalopathy incidences, interleukin (IL)-6/IL-10 ratios and C-reactive protein levels than did patients with PAs <= 4.9 degrees (P <= 0.05). Forty-eight (35.80%) patients died due to cirrhosis, with a median of 18 mo (interquartile range, 3.3-25.6 mo) follow-up until death. Thirty-one (64.60%) of these patients were from the PA <= 4.9 degrees group. PA <= 4.9 degrees significantly and independently affected the mortality model adjusted for Model for End-Stage Liver Disease score and age (hazard ratio = 2.05, 95% CI: 1.11-3.77, P = 0.021). In addition, Kaplan-Meier curves showed that patients with PAs <= 4.9 degrees were significantly more likely to die. CONCLUSION In male patients with cirrhosis, the PA <= 4.9 degrees cutoff was associated independently with mortality and identified patients with worse metabolic, nutritional, and disease progression profiles. The PA may be a useful and reliable bedside tool to evaluate prognosis in cirrhosis.
- Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells(2015) RAVACCI, Graziela Rosa; BRENTANI, Maria Mitzi; TORTELLI, Tharcisio Citrangulo; TORRINHAS, Raquel Suzana M. M.; SANTOS, Jessica Reis; LOGULLO, Angela Flavia; WAITZBERG, Dan LinetzkyIn breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fatty acids (FA), as well as increased activation of ""de novo"" FA synthesis (FASN). We further investigate whether this lipogenesis reprogramming might be regulated by mTOR/PPAR gamma pathway. Inhibition of the mTORC1 pathway markers, p70S6 K1, SREBP1, and LIPIN1, as well as an increase in DEPTOR expression (the main inhibitor of the mTOR) was detected in HB4aC5.2. Based on these results, a PPAR gamma selective antagonist, GW9662, was used to treat both cells lines, and the lipogenic genes remained overexpressed in the HB4aC5.2 but not HB4a cells. DHA treatment inhibited all lipogenic genes (except for FABP4) in both cell lines yet only induced death in the HB4aC5.2 cells, mainly when associated with trastuzumab. Neither trastuzumab nor GW9662 alone was able to induce cell death. In conclusion, oncogenic transformation of breast cells by HER2 overexpression may require a reprogramming of lipogenic genetic that is independent of mTORC1 pathway and PPAR gamma activity. This reprogramming was inhibited by DHA.