Recém-nascidos com Síndrome de Down (SD) podem apresentar uma proliferação transitória de células imaturas no sangue periférico e medula óssea. A leucometria pode estar muito elevada, impossibilitando o diagnóstico diferencial com leucemia mielóide aguda (LMA). Em contraste com a LMA, a SMT regride espontaneamente em quatro a oito semanas. Objetivo: Apresentar uma criança com SD, SMT e fibrose hepática, que resultou num prognóstico desfavorável. Relato do Caso: D.M.S., masculino, estigmas da SD, hepatoesplenomegalia, sopro sistólico. Hemograma: 95.000 leucócitos/mm³, 19% blastos, 170.000 plaquetas/mm³, hemoglobina 16,2g/dL. Bilirrubina total 35,86 mg/dL, GOT 184 UI, GPT 122 UI. Ecocardiograma: canal átrio-ventricular total, hipertensão pulmonar, persistência do canal arterial. Sorologias negativas. Biópsia hepática: colestase, fibrose portal e sinusoidal, elementos mielóides imaturos. Após normalização da leucometria, manteve plaquetopenia e disfunção hepática. No 50º dia de vida, quimioterapia com Daunoblastina e Citarabina. Evoluiu com pneumonia e insuficiência renal. Óbito no 61º dia. Comentários: A história natural da SMT gera questões intrigantes a respeito de sua origem, evolução e desenvolvimento de leucemia subseqüente. A disfunção hepática e a fibrose têm impacto prognóstico. Em relato anterior, de cada oito casos de SMT com disfunção hepática, seis evoluíram para óbito, sendo que fibrose hepática difusa, associada a eritropoese extramedular, foi encontrada em quatro casos. Acredita-se que a lesão hepática resulta da produção de citocinas pelos megacariócitos, por ser o fígado o segundo órgão hematopoético de células anormais, após a medula óssea.
e11505 Background: We have previously shown that alkylating agent based chemotherapy regimens (AQT) could induce MIS in the PBMNF of BC patients in parallel to a decrease in the expression of the protein hMSH2 in these cells (Fonseca et al., 2005, Breast Cancer Res, 7, R28–32). Since plasma DNA derives mainly from tumor cells, we wanted to know if chemotherapy would also produce MIS in tumor DNA and if this phenomenon could be reproduced in vitro. Methods: 33 previously untreated female BC patients with a mean age of 51 years received AQT(16 ACT;3FAC;2 TAC;1FEC;10AC). Samples from 3 additional patients who received Fulvestrant only as neoadjuvant therapy were also included. Blood (pfDNA and PBMNNF) and urine (ufDNA) were evaluated at time 0,3 and 6 months with 6 MIS markers (BAT40,BAT26, MR2,TP53 PCR15.1, APC and ALU). Levels of fpDNA and fuDNA were measured by spectrophotometry. We incubated in vitro cultures of MCF- 7 cells and PBMNF cells with M at a dose of 0.7μg/ml for 30 minutes with and without A at 20% of the M dose and evaluated serially for 48 hours for MIS and hMH2 expression by immunohistochemistry. Results: We observed at least one MIS event in the PBMNF, fpDNA or fuDNA in 87%, 80% and 80% of the patients, respectively, mainly in BAT40 and BAT 26 markers. There was only 14.74% of concordance of MIS alterations between PBMNF and fpDNA and 8. 42% between fpDNA and fuDNA. Patients receiving Hormones also exhibited MIS. Interestingly, fpDNA levels increased significantly in patients with measurable disease who responded to therapy (47.4 ± 13.34 vs 14.37± 5.32; p = 0.021). In vitro, incubating MCF-7 cells and normal PBMNF cells with M ±A, we observed that we could induce MIS in both MCF-7 cells and normal PBMNF cells but A prevented MIS only in normal PBMNF cells. In normal PBMNF cells without A that sustained MIS there was a significantly decreased percentage of cells expressing hMSH2 ( 96% vs 57% p < 0.001). Conclusions: We conclude that Chemotherapy as well as Fulvestran can induce MIS in normal and malignant cells and that in vitro these effects could be reproduced by treatment with M and prevented in normal cells by A. No significant financial relationships to disclose.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.