Navegando por Palavras-chave "Osteosarcoma"

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    Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma
    (Wiley-Blackwell, 1999-08-01) Petrilli, Antonio Sergio [UNIFESP]; Kechichian, Rita [UNIFESP]; Broniscer, Alberto [UNIFESP]; Garcia, Reynaldo Jesus [UNIFESP]; Tanaka, Cristiana [UNIFESP]; Francisco, J. [UNIFESP]; Lederman, Henrique [UNIFESP]; Odone Filho, Vicente; Camargo, Olavo Pires de; Bruniera, Paula; Pericles, Pedro; Consentino, Elio; Ortega, Jorge A.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Fac Med Santa Casa São Paulo
    Background. Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. Procedure. We tested the activity and toxicity of two cycles of intraarterial carboplatin as a window therapy (600 mg/m(2) per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). Results. Patients' age ranged between 8 and 18 years (median age 13 years). Primarytumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 120% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. Conclusions. We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma. (C) 1999 Wiley-Liss, Inc.
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    Análise dos genes CYP1A2, CYP3A4 e CYP3A5 na resposta à quimioterapia, no processo de tumorigênese e no microambiente metastático do osteossarcoma
    (Universidade Federal de São Paulo (UNIFESP), 2016-02-26) Paolillo, Alini Trujillo [UNIFESP]; Toledo, Silvia Regina Caminada de [UNIFESP]; http://lattes.cnpq.br/8408786810979968; http://lattes.cnpq.br/1936707305114069; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Osteosarcoma (OS) derives from primitive mesenchymal cells and it is the most common malignant bone tumor in children and adolescents. OS treatment still using the same drugs since 1980s and survival rates have not improved since then, wherefore translational research is required to identify targets for novel treatment modalities Purpose: The present study investigated the expression of CYP (Cytochrome P-450) genes in OS, and if they play important role in treatment response and microenvironment to OS establishment, since the CYP enzymes mediate the metabolic activation of precarcinogens and participate in the inactivation and activation of anticancer drugs. The aim also was investigated if chemotherapy modulates CYP genes expression in OS cell lines. Methods: We investigated the expression of CYP1A2, CYP3A4 and CYP3A5 genes in 135 OS samples, including biopsy, bone tumor resection specimens, bone tumor adjacent (nonmalignant tissue), metastasis and lung adjacent to metastasis (nonmalignant tissue) samples. We used bone and lung normal tissues as control, obtained by healthy individuals and purchased. We also investigated in OS cell lines (Saos-2, MG-63, KHOS, U2-OS and M-OS) the modulation of CYP expression by chemotherapy drugs (cisplatin, doxorubicin and methotrexate) used in OS treatment. Results: The adjacent lung samples presented higher CYP1A2 gene expression than control of lung tissue (p=0.0256). The biopsy samples presented lower CYP3A4 gene expression than control of bone tissue (p=0.0314). The high CYP1A2 and CYP3A4 genes expression in bone tumor resection specimens were correlated with better event free-survival (p=0.0244) and good response (p=0.0484), respectively. Moreover, the high gene expression of CYP1A2, CYP3A4 and CYP3A5 were associated with toxicity events, such as infection, mucositis, fever, diarrhea, nephrotoxicity and hepatotoxicity. Furthermore, the chemotherapy drugs upregulated the CYP expression in OS cell lines. Conclusions: Our findings suggest that CYP genes play an important role in OS tumorigenesis, in primary and metastatic sites, as well in response to treatment.
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    Avaliação da ressecção de metástases pulmonares em pacientes com osteossarcoma operados no período de 2005 a 2015
    (Universidade Federal de São Paulo (UNIFESP), 2018-08-02) Reis, Alcania Walburga de Souza Pereira dos [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; http://lattes.cnpq.br/7171708417124895; http://lattes.cnpq.br/1117547169471860; Universidade Federal de São Paulo (UNIFESP)
    Introdução: o osteossarcoma (OS) é o tumor maligno primário ósseo mais comum na infância e na adolescência. O pior fator prognóstico associado à doença é a presença de metástase ao diagnóstico. Dentre os pacientes com doença metastática, há tendência a melhor resposta ao tratamento com cura através de ressecção completa quando há presença apenas de lesões pulmonares. Objetivos: avaliar o impacto da ressecção de nódulos pulmonares em pacientes com suspeita de metástase de OS Métodos: revisão de banco de dados de 36 pacientes com OS metastático diagnosticados no período de 2005 a 2015 no IOP/GRAACC/UNIFESP. Resultados: dentre os 36 pacientes incluídos no estudo, 19,4% foram considerados inoperáveis ao diagnóstico. Dos 29 pacientes operados, 9 (30%) pacientes apresentaram lesões falso positivas. No procedimento cirúrgico foram ressecados 266 nódulos, sendo que apenas 43,6% destes nódulos haviam sido diagnosticados na tomografia de tórax, mostrando que a ressecção cirúrgica foi 3,4 vezes superior na identificação dos nódulos em relação ao exame de imagem. Dos 29 pacientes operados, 48,2% tinham nódulo único (incluindo nódulos menores que 0,5 cm até maiores que 1cm) com diagnóstico de metástase de OS em 70% destes após o procedimento. A taxa de sobrevida global na nossa população foi de 52,3 meses e, quando excluídos os falso-positivos, a estimativa média de sobrevivência foi de 41 meses. Documentamos também que ser verdadeiramente metastático apresenta risco de óbito 8,08 vezes maior que não ser metastático. Quando analisamos os pacientes recidivados, quase 50% destes que puderam ser abordados 3 ou mais vezes tiveram taxa de sobrevida global superior ao grupo que não conseguiu ser abordado cirurgicamente. Conclusões: Nosso trabalho mostrou que os pacientes que ressecaram completamente as lesões pulmonares tiveram importante impacto na taxa de sobrevida global em relação aqueles que não operaram. Mostramos ainda que a taxa de falso-positivo é ao redor de 30%. Contudo, novos protocolos de tratamento para o OS na tentativa de melhorar as curvas de sobrevida devem elaborar novas estratégias que reduzam os falsos-positivos e aumentem a sensibilidade diagnóstica.
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    C-kit expression in human osteosarcoma and in vitro assays
    (E-century Publishing Corp, 2011-01-01) Miiji, Luciana Nakao Odashiro [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Di Cesare, Sebastian; Odashiro, Alexandre Nakao [UNIFESP]; Burnier, Miguel Noel Nascente [UNIFESP]; Toledo, Silvia Regina Caminada de [UNIFESP]; Garcia, Reynaldo Jesus; Alves, Maria Teresa de Seixas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); McGill Univ; Ctr Hosp Afillie Univ Quebec
    Biologic agents targeting oncogenes have encourage researchs trying to correlate the role of tyrosine kinase in the pathogenesis of tumours. Osteosarcoma is a high grade aggressive neoplasm with poor survival. Our aim was to investigate c-kit immunoexpression, its prognostic relevance for patients with osteosarcoma, and the effect of imatinib mesylate (STI571) on proliferation and invasion of the human osteosarcoma cell line. A retrospective immunohistochemical study was performed on archival formalin-fixed paraffin-embedded specimens from 52 patients with high-grade primary osteosarcoma of extremities treated at the Pediatric Oncology Institute (IOP, GRAAC) and archived in the Department of Pathology, Federal University of Sao Paulo. Only pre-chemotherapy specimens were analyzed. Strongly stained cytoplasm and membrane cells were taken as positive. Human osteosarcoma cells from line MG-63 were incubated and the inhibitory effect of imatinib mesylate (STI571) on cell proliferation and invasion was studied. In 24 cases (46.15%), c-kit was expressed by the cells and c-kit-positive tumors exhibited lower necrosis post-chemotherapy. No correlation was found between c-kit expression and overall and disease-free survival. Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but not the invasive capacity of these neoplastic cells. These data suggested that imatinib mesylate could be a therapeutic target of strategies against osteosarcoma tumors. Further studies are necessary to confirm this indication.
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    Cardioprotective effect of dexrazoxane during treatment with doxorubicin: A study using low-dose dobutamine stress echocardiography
    (Wiley-Blackwell, 2005-12-01) Paiva, Marcelo Goulart [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Moises, Valdir Ambrosio [UNIFESP]; Macedo, Carla Renata Pacheco Donato [UNIFESP]; Tanaka, Cristiana [UNIFESP]; Campos, Orlando [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); GRACC
    Aim. To assess the late cardioprotective effect of dexrazoxane associated with doxorubicin during treatment of osteosarcoma by means of low-dose dobutamine stress echocardiography (LDDSE) in non-relapsed asymptomatic children and teenagers.Patients and Methods. the study population included 58 patients with osteosarcoma divided in three groups, with equivalent age range, gender proportion and body surface area. Group I (21 patients, 14 males, 15 +/- 4 years) was analyzed before chemotherapy and considered the control group; Group II (19 patients, 11 males, 19.7 +/- 4 years) was treated with 348.4 +/- 18 mg/m(2) of doxorubicin only and Group III (18 patients, 14 male, 16.8 +/- 5 years) treated with 396.5 +/- 55 mg/m(2) of doxorubicin with dexrazoxane in the ratio 10:1. the patients were submitted to LDDSE (maximal dose 5 mu g/ kg/min). No major side effects were observed. Heart rate, blood pressure, left ventricular diameters, end systolic wall stress (ESWS), and other diastolic and systolic function indexes were assessed at rest conditions and during LDDSE and compared between the three groups.Results. Group III received a doxorubicin dose significantly greater than Group II (P = 0.001). During LDDSE there were no significant changes in the diastolic function indexes in any of the groups, but there was a significant increase of systolic indexes and a decrease of ESWS in Group III compared to group II. There was no significant difference of any systolic functional parameters between Group I and III. Considering the ejection fraction (EF) at rest or at LDDSE, 13 patients (69.4%) in Group II and 5 patients (27.7%) in Group III were considered to have systolic dysfunction. (P = 0.02).Conclusion. Myocardial response to LDDSE in patients treated with doxorubicin and dexrazoxane was similar to patients without chemotherapy and better than those treated with doxorubicin only, suggesting less cardiotoxicity.
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    Clinicopathologic study and Ki-67 proliferative marker evaluation in human osteosarcomas
    (Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2005-12-01) Marinho, Larissa Cardoso [UNIFESP]; Patricio, Francy Reis da Silva [UNIFESP]; Garcia Filho, Reynaldo Jesus [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Odashiro, Luciana Nakao [UNIFESP]; Macedo, Carla Renata Pacheco Donato [UNIFESP]; Alves, Maria Teresa de Seixas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de Brasília
    BACKGROUND: Osteosarcoma is a relatively uncommon malignant neoplasm and little information has been reported on its cell proliferation using Ki-67. OBJECTIVES: Evaluate histological, clinical and immunohistochemical parameters using Ki-67 labeling index (LI), correlate one to another and with follow-up. MATERIAL AND METHOD: Fifty-seven patients with available clinicopathological data submitted to the study of cell proliferation as determined by Ki-67 expression measured by immunohistochemistry (IHC) staining using formalin-fixed paraffin embedded sections. In each sample, positive cells were quantified on at least a thousand nuclei and expressed as Ki-67 LI according to median value. RESULTS AND DISCUSSION: Non-significant correlations were observed in metastatic and non-metastatic cases when variables as surgery, tumor size, death and relapse were compared with Ki-67 LI values (cut-off of 45%). In the group of non-metastatic cases there was a direct correlation between higher values of Ki-67 index and better overall survival. Metastatic patients overall survival curve and LI high and low Ki-67 did not show significant differences. CONCLUSION: Based on our results the Ki-67 LI could be useful as a prognostic marker in patients without metastasis at diagnosis.
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    Complicações das endopróteses em pacientes com tumores ósseos do joelho
    (Sociedade Brasileira de Ortopedia e Traumatologia, 2011-01-01) Moraes, Vinícius Ynoe de [UNIFESP]; Gracitelli, Guilherme Conforto [UNIFESP]; Rezende, Fernando Cury [UNIFESP]; Peccin, Maria Stella [UNIFESP]; Viola, Dan Caraí Maia [UNIFESP]; Garcia Filho, Reynaldo Jesus [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Non-conventional endoprostheses (NCE) are frequently used in orthopedic oncology. The complications associated with this procedure have prompted research, due to the fact that it is commonly performed on young patients, with a higher survival rate. We conducted a systematic review of the literature, searching for the best scientific evidence on the subject. The research was carried out in the following databases: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of randomized controlled trials (CCTR), seeking to identify studies that report complications, and compare patellar resurfacing versus retention. The studies were selected according to the best methodological quality that exists for the subject. One hundred and forty six (146) studies were evaluated. No randomized clinical trial was found. We conducted a qualitative and quantitative evaluation of the work found (evidence levels IV and V). We used the Mann-Whitney U test for the statistical analysis. The results indicate a need for further studies that will enable us to reach a more solid conclusion. The rate of complications after NCE can be considered high, despite the low quality of the studies, as demonstrated by the studies that exist in the literature.
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    Correlação clínico-anátomo-patológica e imuno-expressão do HER-2 em osteossarcomas humanos
    (Universidade Federal de São Paulo (UNIFESP), 2003) Miiji, Luciana Nakao Odashiro [UNIFESP]; Alves, Maria Teresa de Seixas [UNIFESP]
    Osteossarcoma e o tumor maligno mais comum em criancas e adultos. E um tumor raro e, apesar de amplamente estudado, apenas o estadiamento da doenca e a localizacao do tumor (axial/pelvica e extremidades) sao fatores prognosticos relevantes no momento do diagnostico. Histologicamente, apenas a necrose pos-qumioterapia tem valor prognostico nos tumores de alto grau, nao havendo portanto, como identificar, no momento do diagnostico, aqueles pacientes que poderao evoluir pior ou que responderao mal ao tratamento quimioterapico convencional. Estudaram-se retrospectivamente 96 osteossarcomas discriminando-se aspectos clinicos e histologicos. Desses pacientes, foram selecionados 64 osteossarcomas pediatricos onde se encontrou que o tamanho do tumor (igual ou maior que 12 cm), o tipo de tratamento cirurgico (radical) e a presenca de anaplasia se correlacionaram com pior sobrevida global. Dos pacientes pediatricos, possuiamos 46 casos localizados em extremidades, nao metastaticos, com especimes pre-qumioterapia. Nesses pacientes pesquisou-se a imunoexpressao do HER-2 pelo metodo da estreptavidina-biotina-peroxidase correlacionando com parametros clinicos e histologicos (idade, sexo, localizacao do tumor, tratamento cirurgico e quimioterapico, subtipo histologico com enfase no componente condroblastico, indice mitotico e necrose pos-quimioterapia). Utilizou-se para essa correlacao o teste do QuiQuadrado de Pearson (variaveis qualitativas) e o teste t-student (variaveis numericas). Fixou-se dois eventos de interesse: obito e metastase que foram analisados utilizando-se o metodo Kaplan-Meier e o teste de LogRank. Na nossa amostra, houve imuno-expressao desse anticorpo em 36,95 por cento dos casos. A positividade para o c-erbB-2 nao influenciou nas curvas de sobrevida global e sobrevida livre de doenca. A imuno-expressao do HER-2 nao se correlacionou com a resposta a quimioterapia, nem com os demais parametros clinicos e histologicos
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    Correlação do tipo de biópsia e sua validade diagnóstica nos tumores músculo-esqueléticos em distintas topografias
    (Sociedade Brasileira de Ortopedia e Traumatologia, 2008-02-01) Siqueira, Karina Levy [UNIFESP]; Viola, Dan Carai Maia [UNIFESP]; Garcia Filho, Reynaldo Jesus [UNIFESP]; Gracitelli, Guilherme Conforto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE:The purpose of this study is to evaluate trephine biopsies with Jamshidi needle performed at the Oncologic Orthopedics Service at UNIFESP/EPM, in musculoskeletal tumors in different locations, in order to propose an effectiveness classification of biopsy categories. METHODS: A retrospective analysis was made of 107 patients that had been submitted to biopsy with the Jamshidi needle and later to a tumor resection followed by an anatomopathological exam of the surgical specimen. Mean age of the patients was 23.5 years (2.7 to 68.7 years). Regarding gender, 40.2% were female, and 50.8% male. In this series, 86 had bone tumor (80.4%) and 21 had soft tissue tumors (19.6%). With respect to location, tumors were found mainly in the lower limbs (72%), followed by upper limbs (22.4%), and pelvis (5.6%). A joint proposal was prepared to classify biopsy categories according to the excellent, good, regular, and poor result. RESULTS: General data analysis showed excellent results in 80.4% of the biopsies, good results in 8.4%, regular in 2.8%, and poor in 8.4%. Adding together excellent and good results, one has 88.8% of the cases. In the series, the authors found 3.7% of complications, and in no case the biopsy served to rule out conservative surgery with preservation of the limb. CONCLUSION: Biopsies with Jamshidi needle represented quite an efficient diagnostic method for musculoskeletal lesions, with low rate of complications and good results comparable to those of open biopsies.
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    Ensaio Clínico Randomizado para avaliar o impacto da adição de quimioterapia metronômica na sobrevida livre de eventos de pacientes recém-diagnosticados com osteossarcoma de alto grau, ressecável, de extremidade, não metastático: Uma colaboração do Grupo Latino Americano para Tratamento de Osteossarcoma
    (Universidade Federal de São Paulo (UNIFESP), 2021) Senerchia, Andreza Almeida [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Universidade Federal de São Paulo
    The aim of this study was, therefore, to analyze whether the addition of cyclophosphamide and methotrexate to a metronomic chemotherapy regimen as maintenance therapy after postoperative methotrexate, adriamycin and cisplatin would improve event-free survival in patients with non-invasive osteosarcoma. metastatic of the extremities. Cyclophosphamide and methotrexate were selected as metronomic agents because of their availability, presumably low toxicity, low cost, and preliminary data suggesting multisegment therapeutic effects.
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    Establishment and cytogenetic characterization of a cell line from a pulmonary metastasis of osteosarcoma
    (Springer, 2013-05-01) Salinas-Souza, Carolina [UNIFESP]; Oliveira, Indhira Dias [UNIFESP]; Oliveira, Renato de [UNIFESP]; Seixas Alves, Maria Teresa de [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Toledo, Silvia Regina Caminada de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Osteosarcoma (OS) is the most frequent malignant bone tumour in children and adolescents. in metastatic patients, the most common site of metastasis is the lung. There are relatively few cell lines of metastatic OS reported in the literature and the cytogenetic aspects of OS metastases are still controversial and inconclusive. Here we describe the establishment of a new OS cell line, M-OS, from a pulmonary metastasis of a typical osteoblastic OS of an 11-year-old boy with metastatic OS at diagnosis. M-OS cells have been maintained in culture for over 50 passages for more than 1 year. M-OS was characterized by immunohistochemistry, conventional cytogenetics and fluorescence in situ hybridization (FISH). in order to evaluate in vitro cell modification, the immunohistochemical analysis was performed in three different moments of the cell line: 10th, 30th and 50th passages. the conventional cytogenetic analysis revealed the ploidy of M-OS cell line as near-diploid, with most metaphases hyperdiploid and tetraploid. We found a copy number gain of MDM2 gene as the most frequent alteration in the FISH analysis. the immunohistochemical analysis confirmed that M-OS cell line maintained the osteogenic nature even after all passages for the cell line establishment in vitro.
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    Estudo funcional do gene DUSP1 em linhagens celulares de osteossarcoma
    (Universidade Federal de São Paulo (UNIFESP), 2015-06-24) Lopes, Luana Joyce da Silva [UNIFESP]; Toledo, Silvia Regina Caminada de [UNIFESP]; http://lattes.cnpq.br/8408786810979968; http://lattes.cnpq.br/1111152788684209; Universidade Federal de São Paulo (UNIFESP)
    O osteossarcoma (OS) é o tumor ósseo maligno mais comum em crianças e adolescentes. Apesar dos sutis avanços nos protocolos atuais de tratamento, a presença de metástase ao diagnóstico, a resistência às drogas e a evolução clínica desfavorável, continuam sendo problemas que atingem aproximadamente 50% dos pacientes com OS. Assim, as pesquisas recentes têm se direcionado a um maior entendimento da biologia básica do OS, buscando biomarcadores e alvos terapêuticos que auxiliem no tratamento dos pacientes. A via de sinalização das proteínas cinases ativadas por mitógenos (MAPKs) desempenham um papel importante na regulação de uma variedade de respostas celulares. DUSP1 pertence a uma família de fosfatases responsáveis pela inativação das MAPKs e têm sido associado ao desenvolvimento de doenças, incluindo o câncer. Em um estudo prévio, identificamos que a expressão aumentada do gene DUSP1 em amostras pós-quimioterapia, indicou um pior prognóstico aos pacientes com OS. No presente trabalho, a fim de uma maior compreensão sobre o papel DUSP1 na patogênese do OS, avaliou-se a função do gene DUSP1 em quatro linhagens celulares de OS (KHOS, Saos2, U2OS e MG63) através de uma série de ensaios celulares combinada com a técnica de silenciamento gênico. Os nossos resultados mostraram que a supressão da expressão do gene DUSP1 resultou em diminuição do crescimento celular, proliferação, migração e invasão das células de OS, além de provocar mudanças no perfil de expressão gênica nos diferentes componentes da via das MAPKs (ERK5, JNK e p38). Em resumo, nossos achados sugerem que o gene DUSP1 apresenta um relevante papel na tumorigênese do OS e pode se tornar um atraente alvo terapêutico para novas estratégias de tratamento, melhorando assim, o índice de cura dos pacientes com OS.
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    Immunohistochemical analysis of pdgfr-alpha, pdgfr-beta and c-abl in retinoblastoma: potential therapeutic targets
    (Karger, 2016) Sanft, Debra-Meghan; Worme, Mali Dawn; de Moura, Leticia Rielo [UNIFESP]; Zoroquiain, Pablo; Fernandes, Bruno F.; Antecka, Emilia; Burnier, Miguel N., Jr.
    Background: Our laboratory previously reported that imatinib mesylate (IM) has an inhibitory effect on two retinoblastoma (Rb) cell lines in vitro. Aims: The purpose of this project was to determine the immunoexpression of platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta and c-Abl in 61 human samples of Rb to determine if IM-sensitive receptors are present. Additionally, this paper seeks to establish a correlation between the expression of PDGFR, c-Abl and the histopathological prognosis. Methods: Sixty-one paraffin-embedded Rbs were collected from the Henry C. Witelson Ocular Pathology Registry. PDGFR-alpha, PDGFR-beta and c-Abl immunostaining was performed according to the protocol provided by Ventana Medical System Inc. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve. Results: Overall, c-Abl expression was identified in 50 out of 61 specimens (81.97%), PDGFR-alpha was identified in 20 out of 60 specimens (33.33%) and PDGFR-beta expression was identified in 57 out of 61 specimens (93.44%). Histopathological prognosis was not correlated with immunoreactivity except in the case of PDGFR-beta. Conclusions: Rb is a cancer that expresses PDGFR-alpha, PDGFR-beta and c-Abl, which are known targets of IM. These markers may be responsible for the documented therapeutic effect of IM on Rb cell lines. (C) 2016 S. Karger AG, Basel
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    Impacto do tratamento oncológico na aceitação alimentar e no estado nutricional de pacientes com Osteossarcoma e suas eventuais complicações
    (Universidade Federal de São Paulo (UNIFESP), 2019-07-25) Oliveira, Susiane Gusi Boin E [UNIFESP]; Oliveira, Fernanda Luisa Ceragioli [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Osteosarcoma is the most frequent bone tumor in children, adolescents and young adults. Its treatment consists of high dose chemotherapy (HD-QT) and surgical procedure. The most commonly used HD-QT can lead to complications such as hematological, infectious, gastrintestinal, renal, hepatic and cardiac failure. Studies indicate nutritional status changes during the osteosarcoma treatment and suggest that nutritional status may contribute to surgical complications and toxicities. Objectives: Study the nutritional status of patients with osteosarcoma during HD-QT and the relationship of weight loss with clinical complications and toxicities. Methods: This is a cohort study of patients with osteosarcoma at a pediatric oncology reference center in São Paulo. Sociodemographic, clinical and nutritional data were evaluated. The nutritional status changes during HD-QT was verified and the weight loss of this period was correlated with clinical complications and a score of toxicities. Results: Twenty-six patients, mostly male (57.69%), aged between 10 and 19 years (73.08%), non-metastatic at diagnosis (65.38%) and undergoing conservative surgery (69, 23%) were evaluated. At diagnosis, 69.23% were normal weight. At pre-surgical time was observed a median weight loss of -6.61%, reduction in the overweight prevalence (p = 0.025) compared to the diagnosis, and a higher percentage of individuals with triceps skinfold thickness depletion when compared to the end treatment (p = 0.028). The z- 57 score values of height for age get worse at the end treatment (p=0,026). Moderate correlation was observed between weight loss (before surgical) with the toxicity score (r=-0,54; 0,027). Conclusion: Patients with osteosarcoma exhibited nutritional deficits during HD-QT treatment, that is evidenced by the anthropometric indicators decrease and weight loss at the end of the 2°. cycle HD-QT. The weight loss was correlated with clinical and metabolic complications. Body composition change and decrease on growth was observed after 6°. cicle HD-QT, suggesting association with nutritional status and cancer treatment. Preventive measures should be taken to try to minimize nutritional impairment during this phase.
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    Investigação celular e molecular do Osteossarcoma primário e metastático
    (Universidade Federal de São Paulo (UNIFESP), 2020-08-27) Paolillo, Alini Trujillo [UNIFESP]; Toledo, Silvia Regina Caminada De [UNIFESP]; Universidade Federal de São Paulo
    Objectives: To identify biological and molecular alterations in the primary and metastatic osteosarcoma (OS). Methodology: 1) All specimens obtained from patients admitted at the Pediatric Oncology Institute with OS as suspect, between 2017 and 2019, were immediately processed for cell culture. All primary cell cultures were recorded by photomicrographs and cryopreserved at the Institutional Biobank. 2) The nuclei isolated from OS bulk were loaded into the Chromium controller and sequenced in the NovaSeq by Illumina®. 3) The sequencing of 31 genes, investigated regarding their expression, was performed in 32 paired specimens (primary and metastatic tumors), obtained from 16 patients, of which 11 were investigated regarding gene expression. The library was prepared using the Ion Chef™ Instrument and the sequencing using the Ion GeneStudio S5. 4)The expression of 32 genes were investigated in 80 paired specimens, including primary tumors (pre- and post-chemotherapy) and metastases, obtained from 33 patients. The quantitative real-time PCR (qRT-PCR) was performed, using TaqMan probes. Results and Conclusion: 1) Thirty-one paired primary cell cultures, obtained from different sites and moments of 13 OS patients, were established and cryopreserved at the Institutional Biobank. These paired primary cell cultures could be useful as new model of study to better understanding of tumorigenesis, treatment response and progression in OS. 2) The single nuclei transcriptome from OS bulk has not been successful, due to the difficulty in obtaining integrate RNA after nuclei isolation. 3) In total, 217 variants were identified, 145 unknown effect, 40 synonymous, 29 missense, 2 non-frameshift deletions and 1 not identified effect. The profile regarding the variant’s presence was different in some cases, when comparing the primary and metastatic tumor from the same patient. 4) The metastasis specimens presented higher expression of ABCC1 e ABCC4 and lower expression of ABCC10, ERCC2, MSH2, SLC22A1, SOD1 and TOP2A comparing to the primary tumors. The high expression of ERCC1 and TOP2A, and the low expression of ABCC3, FASLG and SLC22A1 were associated with worse treatment response. The molecular findings may, in the future, contribute to clinical management, as prognostic factors as well as possible therapeutic targets.
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    Investigação genética e citogenética molecular em osteossarcomas
    (Universidade Federal de São Paulo (UNIFESP), 2002) Toledo, Silvia Regina Caminada de [UNIFESP]; Andrade, Joyce Anderson Duffles [UNIFESP]
    O osteossarcoma (OS) e um tumor osseo maligno, derivado do mesenquima primitivo e entre os tumores osseos e o que apresenta maior incidencia em adolescentes.0 pico de ocorrencia e a segunda decada de vida, acometendo com maior frequencia sitios de crescimento rapido, durante o estirao de crescimento. 0 interesse na patologia e biologia do OS tem aumentado consideravelmente, uma vez que entre os tumores solidos da infancia e adolescencia e exemplo proeminente da eficacia do tratamento quimioterapico agressivo. 0 conhecimento dos eventos geneticos relacionados com a genese e os mecanismos de resistencia a drogas desses tumores contribuem para um melhor entendimento da biologia do OS. 0 presente trabalho teve os seguintes objetivos: 1.Investigar a expressao de genes que possam estar envolvidos na resistencia a drogas no OS, na tentativa de contribuir para o conhecimento desse complexo mecanismo. 2. Avaliar as regioes de perda elou ganho de material cromossomico em OS por meio de hibridacao genomica comparativa (CGH).3. Investigar comparativamente, em linhagens celulares de OS a instabilidade cromossomica, avaliada por meio de hibridacao in situ fuorescente (FISH) e os dados de ganho e/ou perda de material cromossomico obtidos por CGH. Nos investigamos o gene de resistencia a multiplas drogas (MDR1), o proto-oncogene ERBB2 e um gene associado a resistencia a cisplatina (CRAb). A relacao entre a expressao do gene MDR1, resposta a quimioterapia e recaida da doenca ainda permanece controversa. A expressao da proteina erbb2 tem sido relacionada a mau prognostico e a proposta e utilizar essa proteina como alvo terapeutico em OS. 0 produto do gene CRAb foi associado a resistencia a cisplatina, porem sem nenhuma investigacao anterior descrita na literatura. Foram estudadas 26 amostras de 20 pacientes portadores de OS e uma amostra de osso normal sem evidencia clinica de doenca ossea. A estrategia de investigacao utilizada foi a combinacao de transcricao reversa - reacao em cadeia da polimerase (RT-PCR). 0 gene MDR1 foi investigado em 24 samples, 63 por cento positivo para a expressao do gene (5 amostras pre-quimioterapia e 10 amostras pos-quimioterapia). 0 gene CRAb foi investigado em 23 amostras, 57 por cento foram positivas (6 amostras pre-quimioterapia e 7 pos-quimioterapia). 0 gene ERBB2 foi investigado em 21 amostras, somente uma teve... (au)
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    The metastatic behavior of osteosarcoma by gene expression and cytogenetic analyses
    (Elsevier B.V., 2013-10-01) Salinas-Souza, Carolina [UNIFESP]; De Oliveira, Renato [UNIFESP]; De Seixas Alves, Maria Teresa [UNIFESP]; Garcia Filho, Reynaldo Jesus [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Toledo, Silvia Regina Caminada de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Osteosarcoma is a malignant bone tumor with high metastatic potential. Metastasis at diagnosis is the most significant prognostic factor in predicting the clinical outcome of osteosarcoma. We compared the gene expression of metastases that were present at the time of initial diagnosis to those developed later in the course of the disease. We used quantitative real-time polymerase chain reaction to evaluate the gene expression of MDM2, CXCR4, RANKL, RB1, and OSTERIX in 98 samples of osteosarcoma taken from 47 patients (74 metastases and 24 primary tumors) and 30 nonmalignant lung tissues surrounding osteosarcoma metastases. in addition, we investigated the copy number changes of RB1 and MDM2 genes in 12 primary cultures of pulmonary metastases of osteosarcoma, using interphase fluorescence in situ hybridization. Metastases from metastatic patients at diagnosis were characterized by low expression of RB1 and RANKL (P = .0009 and P = .0109, respectively) and overexpression of CXCR4 and MDM2 (P = .0389 and P = .0325, respectively). the loss of RANKL and gain of CXCR4 could also be detected in the primary tumors of metastatic patients at diagnosis (P = .0121 and P = .0264, respectively). Thus, some early genetic events such as the loss of RANKL and the gain of CXCR4 expressions probably facilitate the metastatic progression concomitant with the primary tumor establishment, supporting the role of the CXCR4 receptor in directing osteosarcoma metastases to the lung. On the other hand, late events such as the loss of RB1 and gain of MDM2, crucial regulators of cell cycle, appear to be related to the final mechanisms contributing to the metastatic establishment of osteosarcoma. (c) 2013 Elsevier Inc. All rights reserved.
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    Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia
    (Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2008-04-01) Alves, Maria Teresa de Seixas [UNIFESP]; Miiji, Luciana Nakao Odashiro [UNIFESP]; Marinho, Larissa Cardoso [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Garcia Filho, Reynaldo Jesus [UNIFESP]; Tolledo, Silvia Caminada [UNIFESP]; Patricio, Francy Reis da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: Osteosarcomas (OS), the most frequent primary malignant bone tumors, have aggressive local behavior and high rate of metastatization. The events that allow tumor growth and dissemination are still controversial. The studies about carcinogenesis and tumor progression in this neoplasia, which are based on c-erb-B2, P-glycoprotein (P-gp) and p53 immunoexpression, show conflicting results as to the real prognostic value and its correlations with histological parameters. Anaplasia in childhood neoplasias is a histological parameter of tumor aggressiveness and chemoresistance. In primary or metastatic OS, its meaning remains controversial. On the other hand, in other human neoplasias, c-erb-B2 expression is associated with p53, nuclear grade and other aggressiveness parameters. OBJECTIVE: The aim of the present study was to evaluate p53, c-erb-B2 and P-gp immunoexpression in OS, correlating the parameters with the presence of anaplasia. METHODS: This study included 96 pre-chemotherapy biopsies in patients with high-grade OS diagnosed between 1991 and 2000. The immunohistochemical evaluation of p53 and c-erb-B2 was carried out with the streptavidin-biotin-peroxidase technique. Cases were considered positive when there was immunoexpression in 10% or more neoplastic cells. Only membrane staining (for c-erb-B2 and P-gp), and nuclear staining (for p53) were considered positive. Anaplasia was defined as Wilms' tumor, and considered present or absent. RESULTS: Anaplasia was present in 29 out of 82 cases (35.36%); p53 immunoexpression was detected in 25 out of 60 cases (36.23%); P-gp, in 30 out of 73 cases (41.1%); and c-erb-B2, in 22 out of 55 cases (40%). The results demonstrated an association between c-erb-B2 and p53 immunoexpression (p = 0.042), p53 and parameter of anaplasia (p = 0.015), anaplasia and P-gp (p = 0.034). CONCLUSIONS: The p53, c-erb-B2 and P-gp immunoexpression is relatively frequent in high-grade, metastatic and non-metastatic OS. The results reinforce the hypotheses that in the presence of anaplasia adverse events may occur simultaneously in this neoplasm. Anaplasia may become a histological marker for P-gp and/or p53 status in some high-grade OS, and it may indicate chemoresistance. There was no positive association between p53 and P-gp.
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    Postural assessment of patients with non-conventional knee endoprosthesis
    (Sociedade Brasileira de Ortopedia e Traumatologia, 2014-10-01) Nakaya, Luciana; Tsai, Liliana Yu; Garcia Filho, Reynaldo Jesus [UNIFESP]; Petrilli, Marcelo de Toledo; Viola, Dan Carai Maia; Petrilli, Antonio Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective:To investigate the correlation between the sagittal and frontal alignment and possible postural asymmetries found in patients submitted to total knee stent placement for osteosarcoma.Methods:Twenty two individuals were divided into two groups according to tumor location: femur group (13 patients) and tibia group (nine patients), who were evaluated through postural analysis software (SAPO).Results:No statistically significant difference was found between groups, supporting previous result showing that both groups present the same postural asymmetries.Conclusion:We conclude that both groups have the same postural imbalances, especially the knee of the affected limb that presents hyperextension and center of gravity shifted anteriorly and laterally to the non-affected limb, indicating changes in weight bearing and influencing the gait pattern and balance. Level of Evidence II, Prospective Comparative Study.
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    Prognostic factors and outcomes for osteosarcoma: An international collaboration
    (Elsevier B.V., 2009-09-01) Pakos, Emilios E.; Nearchou, Andreas D.; Grimer, Robert J.; Koumoullis, Haris D.; Abudu, Adesegun; Bramer, Jos A. M.; Jeys, Lee M.; Franchi, Alessandro; Scoccianti, Guido; Campanacci, Domenico; Capanna, Rodolfio; Aparicio, Jorge; Tabone, Marie-Dominique; Holzer, Gerold; Abdolvahab, Fashid; Funovics, Philipp; Dominkus, Martin; Ilhan, Inci; Berrak, Su G.; Patino-Garcia, Ana; Sierrasesumaga, Luis; San-Julian, Mikel; Garraus, Moira; Petrili, Antonio Sergio [UNIFESP]; Garcia Filho, Reynaldo Jesus [UNIFESP]; Pacheco Donato Macedo, Carla Renata [UNIFESP]; Seixas Alves, Maria Teresa de [UNIFESP]; Seiwerth, Sven; Nagarajan, Rajaram; Cripe, Timothy P.; Ioannidis, John P. A.; Univ Ioannina; Royal Orthopaed Hosp; Univ Florence; Hosp Univ La Fe; Hop Enfants Armand Trousseau; Med Univ Vienna; Ankara Oncol Hosp; Marmara Univ; Univ Navarra; Univ Navarra Clin; Universidade Federal de São Paulo (UNIFESP); Med Fac Zagreb; Cincinnati Childrens Hosp; Tufts Univ
    We aimed to evaluate the prognostic significance of traditional clinical predictors in osteosarcoma through an international collaboration of 10 teams of investigators (2680 patients) who participated. in multivariate models the mortality risk increased with older age, presence of metastatic disease at diagnosis, development of local recurrence when the patient was first seen, use of amputation instead of limb salvage/wide resection, employment of unusual treatments, use of chemotherapeutic regimens other than anthracycline and platinum and use of methotrexate. it was also influenced by the site of the tumour. the risk of metastasis increased when metastatic disease was present at the time the patient was first seen and also increased with use of amputation or unusual treatment combinations or chemotherapy regimens not including anthracycline and platinum. Local recurrence risk was higher in older patients, in those who had local recurrence when first seen and when no anthracycline and platinum were used in chemotherapy. Results were similar when limited to patients seen after 1990 and treated with surgery plus combination chemotherapy. This large-scale international collaboration identifies strong predictors of major clinical outcomes in osteosarcoma. (C) 2009 Published by Elsevier B.V.