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1.
Ann Hematol ; 102(10): 2815-2822, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37474632

RESUMO

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.


Assuntos
Doença de Hodgkin , Idoso , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Brasil/epidemiologia , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/epidemiologia , Estadiamento de Neoplasias , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento , Vimblastina/uso terapêutico , Idoso de 80 Anos ou mais , Estudos Clínicos como Assunto
2.
Microb Biotechnol ; 14(5): 1976-1989, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34191387

RESUMO

Native hagfish intermediate filament proteins have impressive mechanical properties. However, using these native fibres for any application is impractical, necessitating their recombinant production. In the only literature report on the proteins (denoted α and É£), heterologous expression levels, using E. coli, were low and no attempts were made to optimize expression, explore wet-spinning, or spin the two proteins individually into fibres. Reported here is the high production (~8 g l-1 of dry protein) of the hagfish intermediate filament proteins, with yields orders of magnitude higher (325-1000×) than previous reports. The proteins were spun into fibres individually and in their native-like 1:1 ratio. For all fibres, the hallmark α-helix to ß-sheet conversion occurred after draw-processing. The native-like 1:1 ratio fibres achieved the highest average tensile strength in this study at nearly 200 MPa with an elastic modulus of 5.7 GPa, representing the highest tensile strength reported for these proteins without chemical cross-linking. Interestingly, the recombinant α protein achieved nearly the same mechanical properties when spun as a homopolymeric fibre. These results suggest that varying the two protein ratios beyond the natural 1:1 ratio will allow a high degree of tunability. With robust heterologous expression and purification established, optimizing fibre spinning will be accelerated compared to difficult to produce proteins such as spider silks.


Assuntos
Feiticeiras (Peixe) , Animais , Escherichia coli/genética , Proteínas de Filamentos Intermediários , Proteínas Recombinantes/genética , Resistência à Tração
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