RESUMO
BACKGROUND: Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma (CTCL). Arsenic trioxide (As(2)O(3)) has recently been shown to be effective against leukemias, so we studied whether As(2)O(3) induces apoptosis of CTCL cells in vitro. We further investigated if As(2)O(3) is effective in a MF mouse model. MATERIAL AND METHODS: Annexin V/7-amino-actinomycin-D stainings were carried out to investigate if As(2)O(3) induced apoptosis of CTCL cell lines. To study the underlying mechanisms, the effects of As(2)O(3) on various transcription factors and apoptosis regulating proteins were analyzed by western blots, electrophoretic mobility shift assays and transcription factor enzyme-linked immunosorbent assays. The ability of As(2)O(3) to induce tumor regression was investigated in a MF mouse model. RESULTS: As(2)O(3)-induced apoptosis was paralleled by a reduction of the DNA-binding activities of transcription factors of the NFkB and signal transducer and activator of transcription gene families and reduced expression of the antiapoptotic proteins bcl-1, bcl-xL and mcl-1. Local injections of 200 muM As(2)O(3) into tumors caused complete remissions in five of six mice and one partial remission. CONCLUSIONS: As(2)O(3) induced apoptosis of CTCL cells by the down-regulation of transcription factors that stimulate the expression of antiapoptotic genes. Local injection of As(2)O(3) into MF tumor-bearing mice resulted in tumor regression.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Micose Fungoide/tratamento farmacológico , Óxidos/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Animais , Apoptose/genética , Trióxido de Arsênio , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes bcl-2/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Micose Fungoide/genética , Micose Fungoide/patologia , Proteína de Sequência 1 de Leucemia de Células Mieloides , NF-kappa B/biossíntese , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fator de Transcrição STAT5/biossíntese , Fator de Transcrição STAT5/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Linfócitos T/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética , Proteína bcl-X/biossíntese , Proteína bcl-X/genéticaRESUMO
PURPOSE: To relate different types of radiographic contrast material distributions to anatomic compartments by using cadaveric specimens and to relate the injection site to treatment-induced discomfort and therapeutic effect. MATERIALS AND METHODS: The contrast material distributions of selective nerve root blocks (SNRBs) in 36 patients (13 women, 23 men; mean age, 52 years; age range, 22-88 years) were graded by two radiologists in conference as type 1 (tubular appearance), type 2 (nerve root visible as filling defect), or type 3 (nerve root not visible). These patterns were correlated with pain reduction after 15 minutes and 2 weeks (with a visual analogue scale of 100-mm length). In addition, 30 nerve roots were injected with iodine-containing contrast material and blue dye in three cadaveric specimens. Radiographs were compared with anatomic sections. RESULTS: After 15 minutes and 2 weeks, 75% and 86% of the patients, respectively, reported pain relief. Mean pain relief length after 15 minutes for type 1 distribution was 60 mm; for type 2, 44 mm; and for type 3, 22 mm; and after 2 weeks, it was 34 mm for type 1, 31 mm for type 2, and 57 mm for type 3. There was no correlation between early and late response. Pain during intervention was less pronounced in type 2 injection, compared with type 1 (P = .002). On the basis of anatomic sections, type 1 injection was intraepineural; type 2, extraepineural; and type 3, paraneural. CONCLUSION: Therapeutic SNRB is effective in sciatica, but early response does not predict the effect after 2 weeks. Type 1 injections are more painful than type 2 injections.
