RESUMEN
PURPOSE: To evaluate the efficacy and safety of the combination of ICE (ifosfamide 1.5 g m(-2), carboplatin 100 mg m(-2) and etoposide 150 mg m(-2), days 1-4, q 28 days, G-CSF 5 microg kg(-1) starting from day 6) alone and in combination with regional hyperthermia (RHT) in soft tissue sarcoma (STS) refractory to previous standard doxorubicin-ifosfamide-based chemotherapy. PATIENTS AND METHODS: Twenty patients with advanced STS of different histological sub-types were treated with the ICE regimen with 13 patients receiving additional RHT. A median of four courses of ICE were administered with RHT on days 1 and 3 (60 min, T(max) 42 degrees C). RESULTS: The objective response rate was 20%, with four partial responses (all treated with hyperthermia). In addition, two patients showed mixed responses and five patients stable disease. After a median follow-up time of 15 months, median time to progression was 6 months. Progression free rate estimates were 60% and 45% at 3 and 6 months, respectively. Median overall survival for all patients was 14.6 months. CONCLUSION: These results suggest that ICE alone or combined with RHT shows activity as second-line therapy in doxorubicin-ifosfamide-refractory STS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Etopósido/uso terapéutico , Hipertermia Inducida/métodos , Ifosfamida/uso terapéutico , Sarcoma/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Terapia Combinada/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Resistencia a Antineoplásicos , Etopósido/efectos adversos , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Hipertermia Inducida/efectos adversos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Leucopenia/etiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Terapia Recuperativa/métodos , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Tasa de Supervivencia , Trombocitopenia/etiología , Resultado del TratamientoRESUMEN
HISTORY AND ADMISSION FINDINGS: A 35-year-old man reported progressive exercise dyspnea, decreased exercise tolerance and weight loss of 10 kg in 2 months. Imaging tests demonstrated a tumor of maximally 7 cm diameter in the region of the left atrium. Histologically it was a poorly differentiated leiomyosarcoma G 3, which could not be completely resected (R 2 resection). SUBSEQUENT INVESTIGATION: Six weeks after surgical resection a rapidly growing tumor, maximally 7.5 cm in diameter, was visualized at the right lateral region of the left atrium. It filled it almost completely and extended via the right upper pulmonary vein to the right hilus. TREATMENT AND COURSE: As part of a multimodal therapeutic approach he was given 6 cycles of chemotherapy (doxorubicin and ifosfamide), bringing about significant reduction of the tumor size. The tumor was then completely resected, followed by an orthotopic heart transplantation with right pneumonectomy. The resected surgical specimen indicated complete remission, no vital tumor cells being demonstrated. No tumor recurrence or distal metastasis was seen during a follow-up period of 36 months. The patient died from right heart failure with advanced pulmonary hypertension 45 months after the diagnosis had first been made, 37 months after the cardiac transplantation.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Cardíacas , Trasplante de Corazón , Leiomiosarcoma , Adulto , Terapia Combinada , Doxorrubicina/uso terapéutico , Resultado Fatal , Atrios Cardíacos , Neoplasias Cardíacas/tratamiento farmacológico , Neoplasias Cardíacas/radioterapia , Neoplasias Cardíacas/cirugía , Humanos , Ifosfamida/uso terapéutico , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/radioterapia , Leiomiosarcoma/cirugía , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia/cirugía , NeumonectomíaAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/terapia , Proteínas Proto-Oncogénicas c-kit/genética , Células del Estroma/patología , Benzamidas , Inhibidores Enzimáticos/uso terapéutico , Neoplasias Gastrointestinales/diagnóstico , Terapia Genética , Humanos , Mesilato de Imatinib , Mutación , Piperazinas/uso terapéutico , Pronóstico , Pirimidinas/uso terapéutico , Factores de RiesgoRESUMEN
The enzyme acetyl-CoA: 17-O-deacetylvindoline 17-O-acetyltransferase which terminates vindoline biosynthesis has been isolated from Catharanthus roseus leaves, further characterized and purified to homogeneity by three step column chromatography and subsequent preparative isoelectric focusing. Kinetic properties concerning the enzyme reaction are discussed. Five multiple forms of the acetyl-transferase could be observed, each consisting of two subunits. This enzyme is now the best characterized of the enzymes involved in vindoline biosynthesis.
RESUMEN
From differentiated plants of Catharanthus roseus (L.) G. Don, a specific enzyme was isolated and named acetyl-CoA : 17-O-deacetylvindoline 17-O-acetyltransferase, acting on the biosynthetic formation of the Aspidosperma type alkaloid vindoline.The enzyme shows a high selectivity towards different substrates. The acetyl-CoA-dependent transferase also catalyses the reverse reaction by hydrolysis of the 17-O-acetyl group of vindoline in the presence of free CoA. This enzyme is localized only in vindoline-containing plant parts, but was so far not detectable in cell suspension cultures of C. roseus. The enzyme allows the synthesis of labelled vindoline with high specific activity, applicable for instance as tracer for radioimmunoassays of vindoline.
RESUMEN
From differentiated plants of Catharanthus roseus (L.) G. Don we have isolated a specific enzyme of the vindoline biosynthetic pathway catalysing the S-adenosylmethionine-dependent methylation of 11-O-demethyl-17-O-deacetyl-vindoline. The enzyme we named S-adenosyl-L-methionine : 11-O-demethyl-17-O-deacetylvindoline 11-O-methyltransferase. This transferase exhibits a high substrate specificity. Obviously the O-methylation at C-11 precedes the O-acetylation at the C-17 position during the biosynthesis of vindoline.A second enzyme was detected which hydrolyses the acetyl function of vindoline. The distribution of this acetylesterase in C. roseus plants demonstrates that the enzyme is not specifically associated with the vindoline distribution in the plant material. Most probably this enzyme plays no essential role in the biosynthesis of vindoline.