RESUMO
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBOP2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials. In addition, Snail silencing also reduced resistance to chemotherapy drugs and cancer stem-like properties, such as CD44 expression, aldehyde dehydrogenase (ALDH) activity, colony formation, and in vivo tumour formation and growth. However, radioresistance was not decreased by silencing Snail. Collectively, this study suggested that Snail is a main regulator of the maintenance of malignancy potentials and is a good target to prevent cancer metastasis and to increase chemotherapy susceptibility.
Assuntos
Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Receptores de Hialuronatos/genética , Células-Tronco Neoplásicas/fisiologia , Fatores de Transcrição da Família Snail/genética , Animais , Neoplasias da Mama/patologia , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To investigate the changing patterns of edema, quality of life (QOL), and patient-satisfaction after complex decongestive therapy (CDT) in three trajectories: arm lymphedema (AL), secondary leg lymphedema (LL) and primary leg lymphedema (PL). METHODS: Candidates for AL (n=35), LL (n=35) and PL (n=14) were identified from prospective databases. The patients were treated with CDT for 2 weeks, and lymphedema volume was measured before and immediately following the therapy. Patients then self-administered home therapy for 3 months and presented for a follow-up visit. The Korean version of Short Form-36 (SF-36) was used to assess QOL, and we administered a study-specific satisfaction survey. RESULTS: There was no significant difference in the volume reductions between the 3 groups. There were no significant differences in all of the measures between PL and LL. Overall initial QOL was significantly lower in patients with LL than in patients with AL. SF-36 scores post-CDT did not differ significantly between AL and LL. Clinically significant differences were noted between AL and LL in the mean values of the satisfaction survey. CONCLUSION: AL, LL, and PL may have different longitudinal courses. We suggest that lower extremity lymphedema patients present more favorable outcomes after CDT with respect to QOL and satisfaction than upper extremity lymphedema patients. Clinicians should approach patients with different therapeutic considerations specific to each type or region of lymphedema before using CDT in clinical practice.
RESUMO
OBJECTIVE: To investigate the long-term effects of complex decongestive therapy (CDT) on edema reduction in breast cancer-related lymphedema patients after axillary dissection, according to the initial volume of edema. METHODS: A retrospective review of 57 patients with unilateral arm after an axillary dissection for breast cancer was performed. The patients, treated with two weeks of CDT and self-administered home therapy, were followed for 24 months. Arm volume was serially measured by using an optoelectronic volumeter prior to and immediately after CDT; and there were follow-up visits at 3, 6, 12, and 24 months. Patients were divided into two groups according to the percent excess volume (PEV) prior to CDT: group 1, PEV<20% and group 2, PEV≥20%. RESULTS: In group 1, mean PEV before CDT was 11.4±5.0% and 14.1±10.6% at 24 months after CDT with no significant difference. At the end of CDT, PEV was 28.8±15.7% in group 2, which was significantly lower than the baseline (41.9±19.6%). The reduction of PEV was maintained for 24 months in group 2. CONCLUSION: The long-term effects of CDT were well-maintained for 24 months, but there was a difference in progression of PEV between the two groups. The patients with more initial PEV showed significant volume-reducing effects of CDT. In patients with less initial PEV, the severity of lymphedema did not progress to higher grades.