Craniofaringioma cístico: quimioterapia intratumoral com interferon alfa

OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.OBJETIVO: Avaliar se os craniofaringiomas císticos podem ser controlados com aplicações intratumorais de interferon alfa. MÉTODO: De janeiro de 2002 a abril de 2006, 19 pacientes foram submetidos à colocação de um cateter intracístico conectado a reservatório de Ommaya para aplicações intratumorais de ciclos de 36.000.000 de unidades de interferon alfa. A resposta ao tratamento foi avaliada pelo cálculo do volume tumoral na ressonância magnética de controle ao término de cada ciclo. RESULTADOS: Os pacientes receberam de um a quatro ciclos de quimioterapia. Onze pacientes apresentaram uma redução do volume tumoral maior que 90%; cinco pacientes apresentaram uma redução entre 75% e 90% e três pacientes uma redução menor de 75%. Não houve óbitos durante o tratamento e os efeitos colaterais do inferferon alfa foram bem tolerados. Nenhum tratamento foi interrompido. CONCLUSÃO: A quimioterapia intratumoral com interferon alfa diminui o volume dos craniofaringeomas císticos e pode ser considerada uma nova alternativa terapêutica.Federal University of São Paulo Department of Neurosurgery and Section of Pediatric NeurosurgeryFederal University of São Paulo Department of PediatricsFederal University of São Paulo Laboratory of Pediatric Oncology InstituteUNIFESP, Department of Neurosurgery and Section of Pediatric NeurosurgeryUNIFESP, Department of PediatricsUNIFESP, Laboratory of Pediatric Oncology InstituteSciEL

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.Univ São Paulo, Fac Med, Dept Hematol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Hematol, São Paulo, BrazilUniv São Paulo, Fac Med, Dept Hematol, Lab Citogenet, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Oncol Pediat, São Paulo, BrazilUniv Estadual Paulista, Fac Med Botucatu, Dept Clin Med, Botucatu, SP, BrazilHosp Canc Barretos, Barretos, SP, BrazilCtr Tratamento Fabiana Macedo de Morais, Grp Assistencia Crianca Canc, Grp Cooperat Brasileiro Sindrome Mielodisplas Ped, Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, Dept Hematol, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Oncol Pediat, São Paulo, BrazilWeb of Scienc

Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. In order to better understand the genetic etiology of osteosarcoma, we performed a multi-stage genome-wide association study (GWAS) consisting of 941 cases and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: rs1906953 at 6p21.3, in the glutamate receptor metabotropic 4 [GRM4] gene (P = 8.1 ×10-9), and rs7591996 and rs10208273 in a gene desert on 2p25.2 (P = 1.0 ×10-8 and 2.9 ×10-7). These two susceptibility loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Genome-wide association study identifies two susceptibility loci for osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10⁻⁹) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10⁻⁸ and 2.9 × 10⁻⁷, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Genetics and cytogenetics molecular investigation in osteossarcoma

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)BV UNIFESP: Teses e dissertaçõe

Heteromorfismos Q. caracterização de uma amostra de mongolóides brasileiros e comparação com uma amostra de negróides brasileiros

BV UNIFESP: Teses e dissertaçõe

MAPK7 Gene Controls Proliferation, Migration and Cell Invasion in Osteosarcoma

Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 has been identified as a candidate oncogene, and a promising prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. In this study, we investigated the behavior of MAPK7 gene in OS cell lines. Technical viability, proliferation, migration, invasion, and apoptosis were used to evaluate the function of the MAPK7 gene. We evaluated the behavior of the OS cells with MAPK7 gene silenced, not silenced, and exposed to the main chemotherapy drugs used in OS treatment. We found that silenced MAPK7 gene is effective at suppressing cell proliferation, inhibiting cell migration, and invasion. Furthermore, MAPK7 is an important activator of transcription factors and is the main expression modulator of other key genes in the MAPK pathway. In summary, our study suggests that MAPK7 might be a promising therapeutic target for OS. (C) 2015 Wiley Periodicals, Inc.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Pediatric Oncology Institute IOP-GRAACC/UNIFESPUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Dept Pediat, Rua Botucatu 743,8th Floor, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Dept Morphol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Dept Clin & Expt Oncol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Dept Pediat, Sao Paulo, SP, BrazilDepartment of Pediatrics, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilDepartment of Morphology and Genetics, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilDepartment of Clinical and Experimental Oncology, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilDepartment of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC), Universidade Federal de São Paulo (UNIFESP), São Paulo‐SP, BrazilFAPESP: 2010/10782-8FAPESP: 2011/10459-5Web of Scienc