RESUMO
BACKGROUND: Patients receiving intensive chemotherapy can experience increased distressed related to both the cancer diagnosis and treatment isolation. If not addressed, distress can lead to anxiety, depression, and post-traumatic stress disorder. The purpose of this study was to determine the feasibility and possible benefits of a music imagery intervention for patients hospitalized in a protective environment for the treatment of acute leukemia or high-grade non-Hodgkin's lymphoma. MATERIALS AND METHODS: Adults receiving intensive myelosuppressive chemotherapy in a protective environment were randomized to standard care or standard care plus music imagery. The music imagery sessions occurred twice weekly for up to eight sessions. Patients were encouraged to use the music imagery daily. RESULTS: The principal criteria of feasibility were rate of consent, rate of completion of scheduled sessions, and rate of questionnaire completion. Forty-nine out of 78 patients consented, a 63% consent rate. Seventy-two percent of all scheduled music imagery sessions were completed. The rate of questionnaire completion was 60% with missing data because of illness severity and early discharge. The principal outcomes of benefit (e.g., efficacy) were positive and negative affects, fatigue, and anxiety. Both groups improved over time on all outcomes (all p < 0.001). However, a subgroup of individuals with low baseline negative affect who received the intervention reported significantly less anxiety at discharge than individuals with low baseline negative affect who did not receive the intervention. CONCLUSIONS: Music imagery is feasible for adults with acute leukemia in protected environments. Patients with lower initial distress may benefit from a music imagery program in terms of reduced anxiety at discharge.
Assuntos
Ansiedade/psicologia , Imagens, Psicoterapia , Leucemia/psicologia , Linfoma não Hodgkin/psicologia , Musicoterapia , Doença Aguda , Adulto , Afeto , Idoso , Fadiga , Estudos de Viabilidade , Feminino , Neoplasias Hematológicas , Humanos , Leucemia/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Terapia de Relaxamento , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: c-jun N-terminal kinase (JNK) has been implicated in proliferation and survival downstream from the tyrosine kinase oncogene, p210 BCR-ABL, in chronic myeloid leukemia. We studied whether a similar relationship between JNK and FMS-like tyrosine kinase 3 (Flt3) describes acute myeloid leukemia (AML). METHODS: By immunoprecipitation, Flt3 was found to be activated and identified as the potential origin of JNK activity in a heavy majority of JNK+ve AML blasts tested. Often, Flt3 activity is associated with activating mutation of the gene locus. However, statistical linkage tied JNK activity with Flt3 expression levels rather than with mutation. An adaptor network to describe the signal cascade Flt3-to-JNK was uncovered. RESULTS: Active Flt3 was linked to p85 phosphoinositide-3 (PI-3) kinase, and p85 with cbl and CrkII/CrkL by co-immunoprecipitaton assays from lysates of model cell lines and primary AML blasts. JNK1 co-immunoprecipitated from such lysates with p85-cbl-crkII/L and bound to Crk species SH3 domain in pull-down assay. siRNA-mediated depletion of Flt3 or of cbl, the adaptor at the nexus of this signaling group, inhibited JNK activity on substrate c-jun. Within AML blast cells influenced by Flt3 signaling, selective inhibition of JNK by a small molecule inhibitor, led to proliferative inhibition, apoptosis, and sensitizing cells to the anthracycline, daunorubicin. These effects occurred upon JNK inhibition without off-target inhibition of extracellular signal-regulated kinase or AKT pathways, and p38-kinase activation, an effector in the p53/p14 arf tumor suppressor pathway, was also maintained or augmented. CONCLUSION: JNK is a bonafide signaling pathway from Flt3 in AML whose function for proliferation and survival is required in a significant AML cohort with active Flt3 signaling, by mutation or overexpression of Flt3.