FABIO LUIZ NAVARRO MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
34 resultados
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- Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase(2012) FERREIRA, Adilson Kleber; MENEGUELO, Renato; MARQUES, Fabio Luiz Navarro; RADIN, Adriano; FILHO, Otaviano Mendonca R.; CLARO NETO, Salvador; CHIERICE, Gilberto Orivaldo; MARIA, Durvanei AugustoPhosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes, especially phosphatidylcholine. We recently reported that synthetic Pho-s has potent effects on a wide variety of tumor cells. To determine if Pho-s has a potential antitumor activity, in this study we evaluated the activity of Pho-s against the B16-F10 melanoma both in vitro and in mice bearing a dorsal tumor. The treatment of B16F10 cells with Pho-s resulted in a dose-dependent inhibition of cell proliferation. At low concentrations, this activity appears to be involved in the arrest of the cell cycle at G2/M, while at high concentrations Pho-s induces apoptosis. In accordance with these results, the loss of mitochondrial potential and increased caspase-3 activity suggest that Phos has dual antitumor effects; i.e. it induces apoptosis at high concentrations and modulates the cell cycle at lower concentrations. In vivo, we evaluated the effect of Pho-s in mice bearing B16-F10 melanoma. The results show that Pho-s reduces the tumoral volume increasing survival rate. Furthermore, the tumor doubling time and tumor delays were substantially reduced when compared with untreated mice. Histological analyses reveal that Pho-s induces changes in cell morphology, typical characteristics of apoptosis, in addition the large areas of necrosis correlating with a reduction of tumor size. The results presented here support the hypothesis that Pho-s has antitumor effects by the induction of apoptosis as well as the inhibition of cell proliferation by arrest at G2/M. Thus, Pho-s can be regarded as a promising agent for the treatment of melanoma.
- 11C-PK11195 plasma metabolization has the same rate in multiple sclerosis patients and healthy controls: a cross-sectional study(2021) SOUZA, Aline Morais de; PITOMBEIRA, Milena Sales; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; REAL, Caroline Cristiano; FARIA, Daniele de Paula11C-PK11195 is a positron emitter tracer used for Positron Emission Tomography (PET) imaging of innate immune cell activation in studies of neuroinflammatory diseases. For the image quantitative analysis, it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition (plasma intact fraction). Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition. The purpose of this study is to compare 11C-PK11195 plasma metabolization rate between healthy controls and multiple sclerosis (MS) patients and evaluate the interference of sex, age, treatment, and disease phenotype in the tracer intact fraction measured in arterial plasma samples. 11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients (n = 50) and healthy controls (n = 23) at 20, 45, and 60 minutes after 11C-PK11195 injection. Analyses were also stratified by sex, age, treatment type, and MS phenotype. The results showed no significant differences in the metabolization rate of healthy controls and MS patients, or in the stratified samples. In conclusion, 11C-PK11195 metabolization has the same rate in patients with MS and healthy controls, which is not affected by sex, age, treatment, and disease phenotype. Thus, these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition, by using a population metabolization rate average. The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School (approval No. 624.065) on April 23, 2014.
- Mesenchymal Stem Cells Do Not Prevent Antibody Responses against Human alpha-L-Iduronidase when Used to Treat Mucopolysaccharidosis Type I(2014) MARTIN, Priscila Keiko Matsumoto; STILHANO, Roberta Sessa; SAMOTO, Vivian Yochiko; TAKIYA, Christina Maeda; PERES, Giovani Bravin; MICHELACCI, Yara Maria Correa da Silva; SILVA, Flavia Helena da; PEREIRA, Vanessa Goncalves; D'ALMEIDA, Vania; MARQUES, Fabio Luiz Navarro; OTAKE, Andreia Hanada; CHAMMAS, Roger; HAN, Sang WonMucopolysaccharidosis type I (MPSI) is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of alpha-L-iduronidase (IDUA). Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. For cell transplantation, 4x10(6) MSC-KO-IDUA cells (MSC from KO mice modified with IDUA) were injected into the peritoneum of KO-mice three times over intervals of more than one month. The total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. The antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. The spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of In-111-labeled MSC. In conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases.
- Repeatability of brown adipose tissue activation measured by [18F]FDG PET after beta3-adrenergic stimuli in a mouse model(2023) FARIA, Daniele de Paula; VERA, Cleinando Clemente da Silva; MARQUES, Fabio Luiz Navarro; SAPIENZA, Marcelo TatitThis study aimed to evaluate the repeatability of brown adipose tissue (BAT) activation measured by [F-18]FDG-PET after beta3-adrenergic stimuli with CL316243 in mice.Methods: Male C57BL/6 mice underwent [F-18]FDG-PET at baseline without stimulation (T0-NS), on three consecutive days after intravenous administration of the selective beta 3-adrenergic agonist CL316243 (T1-CL, T2-CL, T3-CL), and without stimuli after 1 and 2 weeks (T7-NS and T14-NS). The standardized uptake value (SUVmax), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were measured in each scanning session, with statistical groupwise comparisons by ANOVA and post hoc Tukey test.Results: SUVmax, BMV, and TBG values showed no significant differences between the three PET scans without stimuli, but were significantly higher after CL316243 administration (p < 0.0001). The mean coefficient of variation (CoV) of PET within individuals was 49 % at baseline but only 9 % with pharmacological stimulation.Conclusions: The study demonstrated that administration of the selective beta 3-adrenergic receptor agonist CL316243 (CL) in mice leads to consistent metabolic activation of brown adipose tissue (BAT), as measured by [F-18]FDG-PET. We also demonstrated metabolic activation by repeated pharmacological challenge, without evidence of hysteresis. Thus, the methods used in the current work should serve for further studies on BAT metabolism in experimental animals, with translational value for clinical research.
article 0 Citação(ões) na Scopus Patentometric analysis as a subsid to the management of technological innovation: a case study in radiopharmaceuticals for cancer(2023) CHAVES, Henrique Koch; SILVA, Julia Maria Brandao da; SILVEIRA, Carla Cristina de Freitas da; MARQUES, Fabio Luiz Navarro; MAGALHAES, Jorge Lima deObjective: Prospect the evolution of patent applications onIdentify, extract, process data, organize and make available technological information in the form of graphical interfaces described in oncology patents containing the radioisotopes gallium-68 (68Ga), copper-64 (64Cu) and zirconium-89 (89Z) in order to understand the development of science and technology in the area.Method: The ORBIT Intelligence® platform from the company QUESTEL® was used to identify, extract, process the data, organize and make available the technological information in the form of graphical interfaces, analysis of the filed patents in force in the last 20 years in the main patent offices in the world.Result: For gallium-68, copper-64 and zirconium-89, respectively, 36, 18 and 10 families of patents containing the search terms described in the methodology were identified. In both cases, China stands out in the number of filed patent applications, depositing 61% of the total analyzed. It was also observed that many of the analyzed documents were deposited by universities, reinforcing the concept of company-university partnership. The results obtained point out that the area of this study continues to grow and the understanding of the information present in the patent documents makes itpossible to reflect on spaces to intensify the development of innovations in the oncology area.Conclusions: The results obtained demonstrate the relevance of information for the management of a country's technological development, which can serve as an efficient method to analyze, compare and monitor research and development activities in cancer and also support the planning processes organizations, as well as supporting public and private health policies.- Technetium glucose complexes as potential cancer imaging agents(2015) DAPUETO, Rosina; AGUIAR, Rodrigo B.; MORENO, Maria; MACHADO, Camila M. L.; MARQUES, Fabio L. N.; GAMBINI, Juan P.; CHAMMAS, Roger; CABRAL, Pablo; PORCAL, WilliamsGLUT's (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue (F-18-FDG) with PET images, worldwide. New glucose analogs radiolabeled with Tc-99m could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. D-Glucose (Tc-99m-IDAG) and 2-D-deoxyglucose (Tc-99m-AADG) organometallic complexes were proposed and studied as potential F-18-FDG surrogates. The glucose complexes were prepared and evaluated as potential cancer imaging agents, in a melanoma tumor model. Iminodiacetic acid (IDA) and aminoacetate (AA) moieties were chosen as chelating system for radiolabeling with Tc-99m. Tumor uptake of the formed complexes was evaluated in B16 murine cell line in vitro and in vivo in melanoma bearing C57BL/6 mice. In vitro and in vivo studies were conducted with F-18-FDG in order to compare the uptake of Tc-99m-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with (TcO4)-Tc-99m to obtain the Tc-99m-IDAG and Tc-99m-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60 min for complexes, Tc-99m-IDAG and Tc-99m-AADG, with 6% and 2%, respectively. Biodistribution studies showed high tumor uptake one hour post-injection, reaching tumor-to-muscle ratios of 12.1 +/- 3.73 and 2.88 +/- 1.40 for Tc-99m-IDAG and Tc-99m-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of Tc-99m-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging.
- Analgesic Effect of Crotalphine in a New Model of Rat Bone Cancer Pain(2012) CURY, Yara; GUTIERREZ, Vanessa P.; BRIGATTE, Patricia; ZAMBELLI, Vanessa O.; PICOLO, Gisele; CARVALHO, Juliana S. de; MARQUES, FabioBackground: Crotalphine (CRP), a peptide first identified and isolated from the South American rattlesnake Crotalus durissus terrificus venom, induces analgesic effect mediated by opioid receptors. The aim of this work is to characterize the analgesic effect of crotalphine in a new model of bone cancer pain induced by inoculation of Walker 256 tumor cells into the rat femoral cavity. Methods: Bone tumor implantation and metastasis were determined by histopathological analysis. Bone metabolic alterations were determined by scintigraphy, using 99mTc-MDP. Femoral images were obtained before and 7, 14 and 21 days after tumor cell injection. Bone cancer pain was characterized by the presence of hyperalgesia (rat paw pressure test) and allodynia (von Frey filaments). Results and Discussion: Photomicrographs analyzed 21 days after injection of tumor cells, demonstrated the presence of tumor cells in the femur of the animals. Incorporation of 99mTc-MDP was significant 7, 14 and 21 days, suggesting the development of tumor on the femoral cavity. Histopathological analysis demonstrated the presence of tumor cells in the lung and spleen, but not in the liver and kidneys of the rats. The results indicate that cells inoculated into femoral bone marrow can spread to some organs, including lymphoid organs. Hyperalgesia and allodynia were detected on days 1, 3, 7, 14 and 21 after cell inoculation. Interestingly, the paw withdrawal threshold in the von Frey test was reduced not only in the ipsilateral hind paw but also in the contralateral one, demonstrating the existence of bilateral allodynia (mirror-image pain). To evaluate the involvement of prostanoids in these nociceptive phenomena, Indomethacin, a cyclooxygenase inhibitor, was administered 3,7,14 and 21 days after tumor cell injection. Indomethacin only partially inhibited hyperalgesia and allodynia induced by bone cancer, indicating the involvement of prostanoids in bone cancer pain. The contribution of prostanoids is more significant within the first 3 days after cell injection. CRP (8μg/kg) administered on day 21, blocked hyperalgesia, allodynia and mirror image pain. The analgesic effect was detected up to 2 days after peptide administration and was blocked by κ-opioid receptor antagonist and partially inhibited by δ-opioid antagonists, indicating the involvement of opioid receptors. Morphine only partially inhibited allodynia and hyperalgesia. Conclusions: Results indicate that injection of tumor cells causes bone cancer and pain. CRP induces a potent and long-lasting antinociception in this model, with higher efficacy as compared to standard analgesic drugs.
- High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity(2021) MAGALHAES, Flavio de Castro; FERNANDES, Tiago; BASSANEZE, Vinicius; MATTOS, Katt Coelho; SCHETTERT, Isolmar; MARQUES, Fabio Luiz Navarro; KRIEGER, Jose Eduardo; NAVA, Roberto; BARAUNA, Valerio Garrone; OLIVEIRA, Edilamar Menezes deOne of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; similar to 200%, P=0.0008), early erythroid progenitor colonies (similar to 300%, P<0.0001) and reticulocytes (similar to 500%, P=0.0007), and reduced erythrocyte lifespan (similar to 50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg(-1).day(-1)). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.
conferenceObject 7-Ketocholesterol loaded-phosphatidylserine liposome induces cell death, autophagy, and growth inhibition of melanoma and breast adenocarcinoma.(2018) FAVERO, Giovani Marino; TORTELLI JR., Tharcisio Citrangulo; FERNANDES, Daniel; PRESTES, Ana Paula; KMETIUK, Louise N. B.; OTAKE, Andreia Hanada; ANDRADE, Luciana N. S.; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; MARQUES, Fabio L. N.; CHAMMAS, Roger- [C-11]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis(2019) CARVALHO, Robert H. F.; REAL, Caroline C.; CININI, Simone; GARCEZ, Alexandre T.; DURAN, Fabio L. S.; MARQUES, Fabio L. N.; MELLO, Luiz Eugenio; BUSATTO FILHO, Geraldo; VRIES, Erik F. J. de; BRITTO, Luiz R. G. de; BUCHPIGUEL, Carlos A.; FARIA, Daniele de PaulaBackground: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis. Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P < 0.0001) and the rhMOG/CFA group (r(2) = 0.46, P < 0.0001). Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.