RESUMEN
Tributyltin hydride-mediated radical reactions of organic halides were successfully carried out in a continuous flow system using a microreactor. The reactions proceeded within a very short period of time, coupled with quickly decomposing radical initiators such as V-65 and V-70. The continuous flow reaction system was applied to gram scale synthesis of a key intermediate for furofuran lignans.
RESUMEN
We report a rare case of adult Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) with an e1a3 fusion transcript. A 25-year-old female consulted our hospital for leukocytosis and thrombocytopenia. She was diagnosed with Ph-positive precursor B cell ALL. The patient's BCR-ABL fusion gene showed the e1a3 transcript. She received bone marrow transplantation (BMT) in the first complete remission (CR). However, the disease relapsed 4 months later, and she received a second BMT in the second CR, which caused lethal venoocculusive disease. The duration of the total clinical course was 18 months. We established a new cell line from the patient's leukemic cells at the time of relapse, which is very rare and useful for study as an atypical Ph-positive ALL model. The literature on Ph-positive leukemia lacking ABL exon 2 was also reviewed.
Asunto(s)
Genes abl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adulto , Preescolar , Exones/genética , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Transcripción Genética/genéticaRESUMEN
We report an interesting case of acute myelogenous leukemia (AML) in a Jehovah's Witness patient. A 61-year-old woman, a Jehovah's Witness, consulted our hospital because of continuous fever and refractory pharyngitis. The white blood cell count was increased with myeloblasts and monoblasts, both of which showed positivity for CD33. The level of WT1 messenger RNA (mRNA) in the bone marrow was 130,000 copies/microg RNA. The patient's diagnosis was AML (M4). Because complete remission (CR) was not obtained with 2 courses of chemotherapy consisting of acrarubicin and cytarabine, we tried gemtuzumab ozogamicin (GO) with informed consent. No major side effects appeared, and CR was obtained after 2 courses of GO, which decreased the WT1 mRNA level to 480 copies/microg RNA. The patient has been in CR for 6 months with ubenimex. This case suggests that GO can be one of the treatment options in similar situations, although it should be used with considerable care.
Asunto(s)
Aminoglicósidos/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Testigos de Jehová , Leucemia Mieloide Aguda/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Citarabina/administración & dosificación , Femenino , Gemtuzumab , Humanos , Recuento de Leucocitos , Persona de Mediana Edad , Compuestos Orgánicos/administración & dosificación , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
We report a rare case of T-cell acute lymphoblastic leukemia (T-ALL) with an aberrant phenotype. A 52-year-old man was admitted to our hospital because of lymph node (LN) swelling in the bilateral neck. A computed tomographic scan showed LN swelling in the mediastinum and a right pleural effusion. The tumor cells in the neck LN showed positivity for cytoplasmic CD3, CD7, CD19, and CD79a, whereas the tumor cells in the bone marrow (BM) showed positivity for CD10 and CD13 in addition to the former 4 antigens. The chromosomes in the BM were normal. Neither T-cell receptor gamma nor immunoglobulin heavy chain rearrangement was detected in the neck LN. We diagnosed this case as T-ALL with an aberrant phenotype and started the standard chemotherapy for ALL. The response was so effective that complete remission (CR) was easily attained. The patient is now under maintenance therapy in the first CR without hematopoietic cell transplantation.
Asunto(s)
Antígenos CD19 , Antígenos CD7 , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Derrame Pleural Maligno/tratamiento farmacológico , Supervivencia sin Enfermedad , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/patología , Humanos , Leucemia-Linfoma de Células T del Adulto/diagnóstico por imagen , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/diagnóstico por imagen , Derrame Pleural Maligno/patología , Radiografía , Inducción de RemisiónRESUMEN
Prognostic assessment is crucial for the management of AML. Although the use of karyotype analysis for risk-stratification is widely accepted, prognosis of AML remains ambiguous, particularly for patients categorized into the intermediate cytogenetic risk group and additional markers are required for an accurate prediction of outcome. For this study, we used multiplex real-time RT-PCR, which can simultaneously quantify WT1 and 10 distinct fusion gene transcripts, to prospectively evaluate the pre-treatment bone marrow findings of 53 de novo AML patients. Five patients with normal karyotype or insufficient metaphases detected by conventional karyotype analysis proved to have AML1-MTG8, CBFbeta-MYH11 or PML-RARalpha fusion transcripts. WT1 overexpression was observed in 92% of the patients, and the levels were significantly higher in the cytogenetic favorable risk group, especially patients with PML-RARalpha. WT1 levels also correlated with the percentage of blasts in bone marrow, especially in cases of core-binding factor leukemia. There was no association between initial WT1 levels and outcome in terms of event-free survival or overall survival. These results suggest that multiplex real-time RT-PCR is rapid and useful for the precise cytogenetic stratification of AML, and that WT1 levels at presentation correlate with several biologic features of leukemia, but have no prognostic significance.
Asunto(s)
Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/genética , Proteínas Recombinantes de Fusión/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética/genética , Proteínas WT1/genética , Adolescente , Adulto , Anciano , Médula Ósea/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. METHODS: MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. PATIENTS OR MATERIALS: From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. RESULTS: Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens. CONCLUSION: The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Procarbazina/uso terapéutico , Vincristina/uso terapéutico , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Compuestos de Nitrosourea/administración & dosificación , Prednisolona/administración & dosificación , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
An 18-year-old man was diagnosed as having lymphoblastic lymphoma in January 1997, and treated with chemotherapy. At the 1st relapse, bone marrow transplantation from HLA-identical sibling was performed in June 1998 with only acute graft-versus-host disease (GVHD). At the 2nd relapse, peripheral blood stem cell transplantation from the same donor was performed in October 2000 with both acute and chronic GVHD, which has continued for 25 months, and complete remission has also been maintained.
Asunto(s)
Trasplante de Médula Ósea , Recurrencia Local de Neoplasia/terapia , Trasplante de Células Madre de Sangre Periférica , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Donantes de Tejidos , Adolescente , Histocompatibilidad , Humanos , Masculino , Inducción de Remisión , HermanosRESUMEN
We report a patient with chronic myelogenous leukemia that responded to imatinib mesilate after relapse of blastic crisis following allogeneic bone marrow transplantation. The patient received an unrelated bone marrow transplantation in the 3rd chronic phase, after which the 3rd blastic crisis occurred 5 months later. Since the case was refractory to chemotherapy at that time, imatinib mesilate (600 mg/day) was given, which resulted in a complete cytogenetical remission (CCR). The CCR has maintained for 11 months.
Asunto(s)
Antineoplásicos/uso terapéutico , Crisis Blástica/tratamiento farmacológico , Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Administración Oral , Adulto , Benzamidas , Esquema de Medicación , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Inducción de RemisiónRESUMEN
On-farm vaccination of chickens against Campylobacter jejuni is considered a potentially effective countermeasure to decrease campylobacteriosis via consumption of contaminated chicken meat, but is not yet available. In this study, 2 groups of Jidori chicks were immunized subcutaneously with a formalin-killed C. jejuni with 2 different adjuvants. Other chicks served as the unvaccinated control group. Both vaccines induced high levels of anti-Campylobacter IgG but did not decrease bacterial excretion in cecal droppings and bacterial load in the liver and spleen after oral challenge with 10(5) CFU of the homologous strain. Further study is needed to address the observed irrelevance and to develop a novel effective vaccine against C. jejuni.
Asunto(s)
Vacunas Bacterianas/inmunología , Infecciones por Campylobacter/veterinaria , Campylobacter/inmunología , Pollos , Enfermedades de las Aves de Corral/prevención & control , Adyuvantes Inmunológicos , Animales , Anticuerpos Antibacterianos/sangre , Campylobacter/clasificación , Infecciones por Campylobacter/prevención & control , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunoglobulina G/sangreRESUMEN
An Ac-Ala-Ala-Ala-NH2 tripeptide was folded into a beta-turn structure even in water through hydrophobic binding by a self-assembled porphyrin cage. The turn conformation of the bound peptide was fully assigned from NOESY measurements and was strongly supported by molecular dynamics simulation. Single mutation experiments and molecular modeling also suggested that CH-pi interactions between methyl groups of Ala residues and porphyrin ligands were important for the stabilization of the turn conformation. Furthermore, we observed the induction of a beta-hairpin structure by encapsulation of a heptapeptide, Ac-Gly-Gly-Ala-Ala-Ala-Gly-Gly-NH2, possessing Ala-Ala-Ala sequence at the middle.
Asunto(s)
Alanina/química , Oligopéptidos/química , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformación Proteica , Pliegue de ProteínaRESUMEN
The absolute structures of some naturally occurring chiral 2-isopropenyl-2,3-dihydrobenzofurans, (+)-remirol (1a), (+)-remiridiol (1b), (+)-angenomalin (2), and (+)-isoangenomalin (3), were studied by respective chiral synthesis. Kinetic resolutions of racemic 2-isopropenyl-2,3-dihydrobenzofurans, 2-isopropenyl-4,6-dimethoxy-2,3-dihydrobenzofuran (4), 4-hydroxy-2-isopropenyl-2,3-dihydrobenzofuran-5-carbaldehyde (8), and 2-isopropenyl-6-(MOM)oxy-2,3-dihydrobenzofuran-5-carbaldehyde (11c), by Sharpless dihydroxylation using (DHQ)(2)AQN or (DHQD)(2)AQN gave the corresponding chiral 2-isopropenyl-2,3-dihydrobenzofurans. Chiral (S)-(+)-4 (99% ee, using (DHQD)(2)AQN) was converted to natural remirol (S)-(+)-1a and then to natural remiridiol (S)-(+)-1b. (S)-(+)-8 (97% ee, using (DHQD)(2)AQN) was converted to natural angenomalin (S)-(+)-2. (R)-(-)-11c (>99% ee, using (DHQ)(2)AQN), was converted to natural isoangenomalin (R)-(+)-3. Thus, the absolute structures of natural remirol (+)-1a and remiridiol (+)-1b and angenomalin (+)-2 were determined to be S, and the structure of natural isoangenomalin (+)-3 was R.
Asunto(s)
Benzofuranos/síntesis química , Apiaceae/química , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Ciclización , Cyperaceae/química , Eupatorium/química , Hidroxilación , Indicadores y Reactivos , Cinética , Ligandos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Plantas/química , Piranos , Espectrofotometría Infrarroja , Espectroscopía Infrarroja por Transformada de Fourier , EstereoisomerismoRESUMEN
This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy- d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkin's lymphoma and three patients with Hodgkin's lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1-2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1-2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24-34 months) while the other six have relapsed (PFS 8-16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1-2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1-2 cycles of therapy as compared with the non-responders (81.2%+/-9.5% vs 35.0%+/-20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma.