RESUMO
We describe a method for monitoring chronic myeloid leukemia (CML) patients treated with imatinib that uses fluorescence in situ hybridization (FISH) to detect BCR-ABL in peripheral blood (PB) granulocytes. First, we compared this method, termed Neutrophil-FISH, with interphase FISH (i-FISH) analysis of bone marrow (BM), i-FISH analysis of PB mononuclear cells, and conventional cytogenetic analysis (CCA) of BM in 30 consecutive CML patients. We found the percentage of BCR-ABL-positive neutrophils as determined by Neutrophil-FISH to correlate best with the percentage of Philadelphia chromosome-positive metaphases in the BM determined by CCA (y = 0.8818x + 5.7249; r(2) = 0.968). We then performed a serial Neutrophil-FISH study of 10 chronic-phase CML patients treated with imatinib and found that the technique could clearly separate imatinib responders from nonresponders within 12 weeks of drug administration. There was a significant difference in the percentages of BCR-ABL-positive neutrophils between responder (mean 3 SD, 18.2% 3 11.8%) and nonresponder (82.4% 3 5.1%) groups at 12 weeks (P < .0001, Student t test).Together with real-time quantitative polymerase chain reaction analysis, Neutrophil-FISH represents another useful method for monitoring CML patients during the primary myelosuppressive stage of imatinib therapy because it is a quick, simple, and reliable method for assessing cytogenetic response.
Assuntos
Antineoplásicos/administração & dosagem , Proteínas de Fusão bcr-abl/biossíntese , Hibridização In Situ , Leucemia Mieloide de Fase Crônica/fisiopatologia , Neutrófilos/metabolismo , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Hibridização In Situ/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Monitorização Fisiológica/métodos , Neutrófilos/patologiaRESUMO
We established a novel human myxofibrosarcoma cell line NMFH-1 and analyzed it with spectral karyotyping and comparative genomic hybridization (CGH). NMFH-1 cells are composed of two different types of cells, small, spindle-shaped mononuclear cells and bizarre multinucleated giant cells, which were maintained in vitro over 200 passages. Xenografted tumor showed typical features of myxofibrosarcoma, which included bizarre multinucleated giant cells. Cytogenetic analyses revealed complex abnormalities, including a t(17;22)(q2?2;q13), which has been found in dermatofibrosarcoma protuberans. Subsequent reverse-transcription polymerase chain reaction revealed that the cell line did not have the COL1A1-PDGFB gene fusion. Significant gains of the 1q12 approximately q23 and 8q13 approximately qter regions and loss of the 9p21 approximately pter and 13q12 regions often found in MFH were observed by CGH analysis. We investigated the origin of multinucleated giant cells in xenografted tumor through DNA in situ hybridization. In this system, the human-specific Alu sequence and the mouse L1 sequence were used as specific cell markers of identity. In situ hybridization revealed neoplastic proliferation of the multinucleated giant cells of human origin.
Assuntos
Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 22/genética , Fibrossarcoma/genética , Células Gigantes/patologia , Proteínas de Fusão Oncogênica/fisiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Proliferação de Células , Colágeno Tipo I/fisiologia , Cadeia alfa 1 do Colágeno Tipo I , Dermatofibrossarcoma/genética , Feminino , Fibrossarcoma/classificação , Fibrossarcoma/patologia , Células Gigantes/química , Células Gigantes/metabolismo , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Nus , Camundongos SCID , Hibridização de Ácido Nucleico , Proteínas Proto-Oncogênicas c-sis/fisiologia , Neoplasias Cutâneas/genética , Cariotipagem Espectral , Translocação Genética , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Sclerosing epithelioid fibrosarcoma is a recently described, rare mesenchymal neoplasm. We report a case of sclerosing epithelioid fibrosarcoma that occurred in the lower leg of a 48-year-old man. The karyotype of the tumor exhibited der(1)t(1;10)(p31;p11), der(10)t(10;17)(p11;q11), and der(17) t(11;17)(?;q11). Rearrangement of 10p11 was also found in one previous reported case of this uncommon tumor.
Assuntos
Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 17/genética , Células Epitelioides/patologia , Fibrossarcoma/genética , Rearranjo Gênico , Neoplasias de Tecidos Moles/genética , Translocação Genética/genética , Aberrações Cromossômicas , Fibrossarcoma/patologia , Humanos , Cariotipagem , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias de Tecidos Moles/patologiaRESUMO
A modified procedure was developed for the measurement of the effective air exchange rate, which represents the relationship between the pollutants emitted from indoor sources and the residents' level of exposure, by placing the dosers of tracer gas at locations that resemble indoor emission sources. To measure the 24-h-average effective air exchange rates in future surveys based on this procedure, a low-cost, easy-to-use perfluorocarbon tracer (PFT) doser with a stable dosing rate was developed by using double glass vials, a needle, a polyethylene-sintered filter, and a diffusion tube. Carbon molecular sieve cartridges and carbon disulfide (CS2) were used for passive sampling and extraction of the tracer gas, respectively. Recovery efficiencies, sampling rates, and lower detection limits for 24-h sampling of hexafluorobenzene, octafluorotoluene, and perfluoroallylbenzene were 40% ± 3%, 72% ± 5%, and 84% ± 6%; 10.5 ± 1.1, 14.4 ± 1.4, and 12.2 ± 0.49 mL min⻹; and 0.20, 0.17, and 0.26 µg m⻳, respectively.