CAMILA MARIA LONGO MACHADO

(Fonte: Lattes)
Índice h a partir de 2011
10
Lattes
ResearcherID
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina

Filtros

Mostrar mais
Limpar filtros

Configurações

Resultados de Busca

Agora exibindo 1 - 10 de 21
  • article 13 Citação(ões) na Scopus
    Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200
    (2015) LINDEGREN, Sture; ANDRADE, Luciana N. S.; BACK, Tom; MACHADO, Camila Maria L.; HORTA, Bruno Brasil; BUCHPIGUEL, Carlos; MORO, Ana Maria; OKAMOTO, Oswaldo Keith; JACOBSSON, Lars; CEDERKRANTZ, Elin; WASHIYAMA, Kohshin; ANEHEIM, Emma; PALM, Stig; JENSEN, Holger; TUMA, Maria Carolina B.; CHAMMAS, Roger; HULTBORN, Ragnar; ALBERTSSON, Per
    The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical alpha-radioimmunotherapy of minimal residual ovarian cancer with At-211-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of Tc-99m-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that Tc-99m-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.
  • bookPart
  • article 3 Citação(ões) na Scopus
    Tocilizumab Labeling with (99m)Technetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma
    (2017) CAMACHO, Ximena; MACHADO, Camila Longo; GARCIA, Maria Fernanda; FERNANDEZ, Marcelo; ODDONE, Natalia; BENECH, Juan; GAMBINI, Juan Pablo; CERECETTO, Hugo; CHAMMAS, Roger; CABRALA, Pablo; RIVA, Eloisa
    Background: Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. Objective: To radiolabel Tocilizumab with (99m)Technetium as a potential imaging agents for MM. Methods: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with Tc-99m. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice. Results: LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of (TcHYNIC)-Tc-99m-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours. Conclusions: Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease.
  • article 11 Citação(ões) na Scopus
    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, Williams
    GLUT'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.
  • article 36 Citação(ões) na Scopus
    Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma
    (2012) ONUCHIC, Ana Claudia; MACHADO, Camila M. L.; SAITO, Renata F.; RIOS, Francisco J.; JANCAR, Sonia; CHAMMAS, Roger
    Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.
  • article 41 Citação(ões) na Scopus
    Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGF beta 1-induced macrophages
    (2014) MACHADO, Camila Maria Longo; ANDRADE, Luciana Nogueira Sousa; TEIXEIRA, Veronica Rodrigues; COSTA, Fabricio Falconi; MELO, Camila Morais; SANTOS, Sofia Nascimento dos; NONOGAKI, Suely; LIU, Fu-Tong; BERNARDES, Emerson Soares; CAMARGO, Anamaria Aranha; CHAMMAS, Roger
    In order to study the role of galectin-3 in tumor angiogenesis associated with tumor-associated macrophages (TAM) and tumor parenchyma, the galectin-3 expression was reconstituted in Tm1 melanoma cell line that lacks this protein. Galectin-3-expressing cells (Tm1G3) and mock-vector transfected cells (Tm1N3) were injected into wild-type (WT) and galectin-3 knockout (KO) C57Bl/6 mice. Tumors originated from Tm1G3 were larger in tumor volume with enlarged functional vessels, decreased necrotic areas, and increased vascular endothelial growth factor (VEGF) protein levels. Galectin-3-nonexpressing-cells injected into WT and KO showed increased levels of transforming growth factor beta 1 (TGF beta 1) and, in WT animals this feature was also accompanied by increased VEGFR2 expression and its phosphorylation. In KO animals, tumors derived from galectin-3-expressing cells were infiltrated by CD68(+) -cells, whereas in tumors derived from galectin-3-nonexpressing-cells, CD68(+) cells failed to infiltrate tumors and accumulated in the periphery of the tumor mass. In vitro studies showed that Tm1G3 secreted more VEGF than Tm1N3 cells. In the latter case, TGF beta 1 induced VEGF production. Basal secretion of VEGF was higher in WT-bone marrow-derived macrophages (BMDM) than in KO-BMDM. TGF beta 1 induced secretion of VEGF only in WT-BMDM. Tm1G3-induced tumors had the Arginase I mRNA increased, which upregulated alternative macrophage (M2)/TAM induction. M2 stimuli, such as interleukin-4 (IL4) and TGF beta 1, increased Arginase I protein levels and galectin-3 expression in WTBMDM, but not in cells from KO mice. Hence, we report that galectin-3 disruption in tumor stroma and parenchyma decreases angiogenesis through interfering with the responses of macrophages to the interdependent VEGF and TGF beta 1 signaling pathways.
  • bookPart
    Microambiente tumoral
    (2022) VIEIRA, Igor de Luna; CERQUEIRA, Otto Luiz Dutra; MACHADO, Camila Maria Longo
  • article 35 Citação(ões) na Scopus
    Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the intracellular copper level, triggering cytochrome c release and caspase activation
    (2013) MATIAS, Andreza C.; MANIERI, Tania M.; CIPRIANO, Samantha S.; CARIONI, Vivian M. O.; NOMURA, Cassiana S.; MACHADO, Camila M. L.; CERCHIARO, Giselle
    Dithiocarbamates are nitrogen- and sulfur-containing compounds commonly used in pharmacology, medicine and agriculture. The molecular effects of dithiocarbamates on neuronal cell systems are not fully understood, especially in terms of their ability to accumulate copper ions inside the cell. In this work, the molecular effects of N,N-diethyldithiocarbamate (DEDTC) were studied in human SH-SY5Y neuroblastoma cells to determine the role of copper in the DEDTC toxicity and the pathway trigged in cell by the complex Cu-DEDTC. From concentration-dependent studies, we found that 5 mu M of this compound induced a drastic decrease in viable cells with a concomitant accumulation in intracellular copper resulted from complexation with DEDTC, measured by atomic absorption spectroscopy. The mechanism of DEDTC-induced apoptosis in neuronal model cells is thought to occur through the death receptor signaling triggered by DEDTC-copper complex in low concentration that is associated with the activation of caspase 8. Our results indicated that the mechanism of cell death involves cytochrome c release forming the apoptosome together with Apaf-1 and caspase 9, converting the caspase 9 into its active form, allowing it to activate caspase 3 as observed by immunofluorescence. This pathway is induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions present in the culture medium and transports them into the cell, suggesting that the DEDTC by itself was not able to cause cell death and the major effect is from its copper-complex in neuroblastoma cells. The present study suggests a role for the influence of copper by low concentrations of DEDTC in the extracellular media, the absorption and accumulation of copper in the cell and apoptotic events, induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions.
  • article 3 Citação(ões) na Scopus
    99mTechnetium-or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents
    (2021) CAMACHO, Ximena; PERRONI, Carolina; MACHADO, Camila L.; CARNEIRO, Camila de Godoi; JUNQUEIRA, Mara de Souza; FARIA, Daniele; GARCIA, Maria F.; FERNANDEZ, Marcelo; ODDONE, Natalia; BENECH, Juan; BUCHPIGUEL, Carlos A.; CERECETTO, Hugo; CHAMMAS, Roger; RIVA, Eloisa; CABRAL, Pablo; GAMBINI, Juan P.
    Background: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. Objective: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. Methods: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37 degrees C, derivatized with NHS-HYNIC-Tfa and radiolabeled with Tc-99m. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. Results: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with Tc-99m via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. Conclusion: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.
  • article 13 Citação(ões) na Scopus
    Technetium-99m-or Cy7-Labeled Rituximab as an Imaging Agent for Non-Hodgkin Lymphoma
    (2017) CARNACHO, Ximena; MACHADO, Camila Longo; GARCIA, Maria Fernanda; GAMBINI, Juan Pablo; BANCHERO, Agustina; FERNANDEZ, Marcelo; ODDONE, Natalia; ZANATTA, Daniela Bertolini; ROSAL, Carolina; BUCHPIGUEL, Carlos Alberto; CHAMMAS, Roger; RIVA, Eloisa; CABRAL, Pablo
    Introduction: Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radio label agent for targeting NHL. Objective:To radiolabel rituximab with technetium-99m (Tc-99m) or Cy7 and evaluate both probes as potential imaging agents for NHL. Methods: Rituximab was derivatized with the trifluoroacetyl hydrazino protected form of succinimidyl ester of HYNIC and radiolabeled with Tc-99m. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and single-pho- ton emission computed tomography/computed tomography (SPECT/CT) were performed. Raji cells were transfected with luciferase for bioluminescent NHL imaging up to 21 days. Rituximab was labeled with Cy7 for in vivo noninvasive fluorescence imaging up to 96 h. Results: Radiolabeling was carried out in a fast, reproducible, easy, and stable way with high radiochemical purity and did not interfere with epitope recognition. Biodistribution and SPECT/CT studies showed high liver and discrete tumor uptake. Bioluminescence and fluorescence studies helped us evaluate rituximab-Cy7 in Raji subcutaneous engraftment in BALB/c nude mice. Conclusions: Our results support the potential use of rituximab labeled either with Tc-99m or Cy7 as a molecular imaging tool for staging, restaging, and guiding surgical excision of tumors, which merits further evaluation. (C) 2017 S. Karger AG, Basel