Clinical features and prognosis of childhood B-lineage acute lymphoblastic leukemia expressing the PRAME gene / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).@*METHODS@#A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors.@*RESULTS@#Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05).@*CONCLUSIONS@#Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.

Valoración clinica del tratamiento oncologico

La metodología clínica en oncología tiene hoy en día una gran utilidad especialmente porque es un instrumento que permite valorar la efectividad de los diversos tratamientos que actualmente se dispone, su importancia es mayor pues ayuda a definir conductas terapeuticas en una especialidad medica que cada día esta sometida a nuevos cambios, El conocimiento de esta rama de oncología es un deber para todo oncologo moderno y la obligación de revisar casuisticas, efectividad de tratamientos, morbimortalidad de los mismos, tasas de sobrevida, le permiten al medico tener una visión global sobre la enfermedad y singular sobre cada paciente, pudiendo adoptar una conducta medica y etica correcta.

Imunoterapia ativa específica e imunoquimioterapia adotiva em tumores experimentais: açäo da interleukin - 2

Uma preparaçäo de proteínas de membrana plasmática de células tumorais obtidas por processo original de vesículaçäo de membrana celular é usada como antígeno específico do tumor. Em sistema singênico protegeu 80% dos camundongos contra inóculo tumoral. Inóculo tumoral jé estabelecido, em início de crescimento, é curado em 70 a 80% com inoculaçäo de antígeno de membrana com afjuvante, em tumores experimentais de camundongo. A imunoterapia adotiva específica, isto é, a transferência de linfócitos pré-sensibilizados, näo protegeu camundongos contra tumor já desenvolvido. A imunoquimioterapia adotiva, transferência de linfócitos de baço de animal imunizados pelo tumor + 1 dose de ciclofosfamida foi eficiente, curando 80% dos animais com tumor singênico já estabelecido, sendo que a ciclofosfamida apenas retarda temporariamente o crescimento tumoral. Este projeto näo tem aplicaçäo clínica, pois para o doente näo se dispöe de linfócitos isogênicos sensibilizados especialmente contra seu câncer. Está sendo tentada a substituiçäo de linfócitos T sensibilizados por "Interleukin-2" + ciclofosfamida. A "Interkeukin-2" é obtida in vitro por açäo de macrófago + linfócito T helper + concanavalina A. Experiência preliminares em tumores experimentais deram nítido retardamento do crecimento dos mesmos. Este produto está sendo purificado e concentrado e produzido especificamente com antígeno do próprio tumor