Navegando por Palavras-chave "Anthracyclines"
Agora exibindo 1 - 2 de 2
Resultados por página
Opções de Ordenação
- ItemSomente MetadadadosDNA damage induced by the anthracycline cosmomycin D in DNA repair-deficient cells(Springer, 2010-04-01) Carvalho, Helotonio [UNIFESP]; Garrido, Leandro M.; Furlan, Renata L. A.; Padilla, Gabriel; Agnoletto, Mateus; Guecheva, Temenouga; Henriques, Joao A. P.; Saffi, Jenifer; Martins Menck, Carlos Frederico; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Univ Fed Rio Grande do SulAnthracyclines have been widely used as antitumor agents, playing a crucial role in the successful treatment of many types of cancer, despite some side effects related to cardiotoxicity. New anthracyclines have been designed and tested, but the first ones discovered, doxorubicin and daunorubicin, continue to be the drugs of choice. Despite their extensive use in chemotherapy, little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines. the anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis, characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene.We assessed the induction of apoptosis (Sub-G(1)) by cosmomycin D in nucleotide excision repair-deficient fibroblasts (XP-A and XP-C) as well as the levels of DNA damage (alkaline comet assay).Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner, with highest apoptosis levels observed 96 h after treatment. the effects of cosmomycin D were equivalent to those obtained with doxorubicin. the broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells, and DNA damage induced by cosmomycin D was confirmed by alkaline comet assay.Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts. Despite similar apoptosis levels, cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin. This may be related to differences in structure between cosmomycin D and doxorubicin.
- ItemSomente MetadadadosA Produção Acadêmica Sobre As Relações Étnico-Raciais Em Livro Didático (2005 - 2015)(Universidade Federal de São Paulo (UNIFESP), 2017-03-29) Santos, Maria Veronica Camara Dos [UNIFESP]; Moises, Valdir Ambrosio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background: Anthracyclines are effective drugs for cancer treatment, but are strongly associated with early or late cardiotoxicity. Left ventricular ejection fraction (LVEF) by echocardiography is recommended for the diagnosis. Left ventricular global longitudinal two-dimensional strain (LVGL2DS) by speckle tracking echocardiography (STE) seems to have high sensitivity. The aim of this study was to analyze the global and segmental LV systolic function and LVGL2DS by STE in patients late after treatment of osteosarcoma. Methods: Survivors of osteosarcoma, treated during adolescence with doxorubicin and epirubicin, according with the protocol at the time of treatment, and a group of healthy controls, participated in this study with clinical and conventional echocardiographic evaluations including LVGL2DS by STE. Subgroup 1, patients had normal LVEF ( 53%), and subgroup 2, abnormal LVEF (< 53%). LVGL2DS was normal if ≤ -18.9 %. Data were analyzed and compared with parametric or nonparametric tests as appropriated; significant if p < 0.05. Results: 26 patients (26.2 years; 13 females) and 13 controls were included in the study. The meantime since treatment was 9.9 ± 2.9 years and doxorubicin cumulative dose was 347 ± 39.6 mg/m². Only one patient included in the study (3.85%) received epirubicin (Study III), and had his cumulative dose converted for doxorubicin model as recommended by the Children’s Oncology Group Guidelines. Twenty patients were in subgroup 1, and 6 in subgroup 2. LVGL2DS was lower in subgroups 1 (-17.6 ± 2.8%) and 2 (-14.5 3.9%) compared to control (-20.4 1.9%) (< 0.01). For all patients, the proportion of cardiotoxicity increased from 6/26 (23%), with LVEF only, to 17/26 (65%) when adding LVGL2DS analysis. The basal segments of septal, anteroseptal and inferior walls were more frequently altered with higher strain values (less negatives, mathematically) than other segments of the same walls. Conclusions: Late after treatment of osteosarcoma, patients had decreased LVGL2DS despite normal LVEF that possibly represents hidden cardiotoxicity. Basal myocardial segments were more affected.