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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 do impacto do uso de maconha no perfil de sintomas e de resposta ao tratamento de pacientes em primeiro episódio psicótico
    (Universidade Federal de São Paulo (UNIFESP), 2019-06-10) Coutinho, Luccas Soares [UNIFESP]; Araripe Neto, Ary Gadelha De Alencar [UNIFESP]; http://lattes.cnpq.br/8107200180236710; http://lattes.cnpq.br/7728454144217028; Universidade Federal de São Paulo (UNIFESP)
    The present dissertation aims to investigate symptomatic and response-totreatment differences in first-episode psychosis (FEP) patients who use and do not use cannabis. The relationship between FEP and cannabis is complex, with results suggesting that: FEP is anticipated by its use in adolescence; a higher risk for psychosis and a possible influence on symptoms presentation. In the present study, we investigated the influence of cannabis use on symptoms, functionality and remission of antipsychotic naïve FEP patients. A total of 175 subjects were enrolled, of whom 99 were reassessed after 10 weeks of treatment. The variables of this investigation were obtained from the following scales: Positive and Negative Syndrome Scale (PANSS); Addiction Severity Index (ASI 6), Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI). The acute use of cannabis (use in the month prior to the first evaluation) had a significant relationship with higher excitement symptoms and less functionality rates in the first evaluation. Positive, negative, and excitement symptom remission rates were significantly higher in subjects who had used acute cannabis. In the second evaluation, no symptomatic differences were found between the two groups of patients. This effect may be related to discontinuation of acute cannabis use after initiation of treatment, or to an intrinsic characteristic of the response profile of these patients. Therefore, the acute use of cannabis was related to worse symptomatic and functional presentations in FEP patients without prior antipsychotic use.