RESUMEN
Quantitative in vitro tests showed that purified preparations of L-asparaginase from Escherichia coli were more toxic to blood lymphocytes from 12 of 15 patients with chronic lymphocytic leukemia than to lymphocytes from 25 persons with normal hemograms. Incubation for 7 days with 10 units per milliliter killed, on the average, 77 percent of leukemic and 34 percent of normal lymphocytes. The reagent produced appreciable toxicity to leukemic lymphocytes after 2 days of incubation.
Asunto(s)
Amidohidrolasas/toxicidad , Linfocitos/efectos de los fármacos , Animales , Técnicas de Cultivo , Escherichia coli , Cobayas , Humanos , Leucemia LinfoideRESUMEN
The hypothesis that interferon may be useful for intractable chronic lymphocytic leukemia (CLL) is based on two incidental findings: first, the similarity in the in vitro radioresistance of the blood lymphocytes of intractable CLL and of hairy cells; secondly, the similarity of the incidence of intractable CLL patients and the incidence of CLL patients who respond to interferon treatment.
Asunto(s)
Interferones/uso terapéutico , Leucemia Linfocítica Crónica de Células B/terapia , Humanos , Modelos BiológicosRESUMEN
The paper is a review of some cancer patients who were treated successfully by surgery followed by chemotherapy. The cases suggest the hypothesis that early cancer growth following surgery is more sensitive to chemotherapy than the active cancer growth of the original tumor.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , División Celular/efectos de los fármacos , Terapia Combinada , Humanos , Modelos Biológicos , Neoplasias/patología , Neoplasias/cirugíaRESUMEN
In four reported studies, intensive chemotherapy of various types was administered to large groups of patients with chronic lymphocytic leukemia (CLL) in advanced stages. About half of the patients were non-responders to the therapy. Resistance to therapy was also found in 12% of patients with early CLL and in 19 CLL patients who had in vitro radioresistant lymphocytes before therapy. The findings support the hypothesis of the heterogeneity of CLL patients and suggest the need for new methods for therapy of non-responders and for in vitro or in vivo tests to diagnose non-responders.
Asunto(s)
Resistencia a Medicamentos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Antígenos Heterófilos , Humanos , Leucemia Linfocítica Crónica de Células B/inmunologíaRESUMEN
About 19-26% of patients with chronic lymphocytic leukemia (CLL) have intractable disease resistant to chemotherapy, have a relatively short median survival time and are responsive to splenectomy. Lymphocytes from patients with intractable CLL are resistant in vitro to X-irradiation and to colchicine. Responsive CLL is an accumulative disease while intractable CLL is a proliferative disease.
Asunto(s)
Resistencia a Medicamentos , Leucemia Linfocítica Crónica de Células B/clasificación , Tolerancia a Radiación , Colchicina , Diagnóstico Diferencial , Humanos , Leucemia Linfocítica Crónica de Células B/etiología , Leucemia Linfocítica Crónica de Células B/terapia , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Inducción de RemisiónRESUMEN
Lymphomas developed in mice treated with X-irradiation. The radiosensitivity of cells of the lymphomas had a bimodal frequency distribution. The cells of 11 lymphomas had approximately the same radiosensitivity as normal murine lymphocytes; 6 lymphomas were highly radioresistant. Radioresistant and radiosensitive lymphomas were analogous to intractable chronic lymphocytic leukemia (CLL) and to responsive CLL in humans. The radioresistant lymphomas can be used to study the effect of therapeutic agents on the animal model for intractable CLL both in vitro and in vivo.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/etiología , Animales , Modelos Animales de Enfermedad , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/radioterapia , Ácidos Linolénicos/uso terapéutico , Linfoma/tratamiento farmacológico , Linfoma/etiología , Linfoma/radioterapia , Ratones , Tolerancia a Radiación , Ácido gammalinolénicoRESUMEN
About 23% of all patients with chronic lymphocytic leukemia (CLL) are resistant to chemotherapy and have intractable CLL. Recent work showed the usefulness of splenectomy for the treatment of ICLL patients. The peripheral blood lymphocytes of ICLL patients were radioresistant in vitro. This reaction provided a diagnostic test for ICLL. Normal lymphocytes are highly radiosensitive but become radioresistant on the addition of phytohemagglutinin or other mitogens. These findings suggest the hypotheses: ICLL arises from splenic lymphocytes which have reacted to an immune stimulus; ICLL is a discrete disease with its own pathogenesis, diagnosis and therapy.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/etiología , Antineoplásicos/uso terapéutico , Resistencia a Medicamentos , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/terapia , Linfocitos/efectos de la radiación , Modelos Biológicos , Tolerancia a Radiación , EsplenectomíaAsunto(s)
Células Sanguíneas , Calor , Leucemia Linfoide/sangre , Leucemia Mieloide/sangre , Leucocitos , Linfocitos , HumanosAsunto(s)
Leucemia Experimental , Leucemia Linfoide , Linfocitos , Animales , Asparagina/metabolismo , Radioisótopos de Carbono , Recuento de Células , Línea Celular , Supervivencia Celular , Células Cultivadas , Medios de Cultivo , Glutamina/metabolismo , Humanos , Lectinas/farmacología , Leucina/metabolismo , Activación de Linfocitos , Linfocitos/metabolismo , Ratones , Proteínas de Neoplasias/biosíntesisAsunto(s)
Supervivencia Celular , Calor , Animales , Células Cultivadas , Cricetinae , Femenino , OvarioAsunto(s)
Asparaginasa/uso terapéutico , Técnicas de Cultivo , Leucemia Linfoide/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Asparaginasa/farmacología , Asparaginasa/toxicidad , Supervivencia Celular , Escherichia coli , Humanos , Leucemia Linfoide/sangre , Leucemia Mieloide Aguda/sangre , Linfoma/tratamiento farmacológico , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/tratamiento farmacológico , Neoplasias Experimentales/tratamiento farmacológicoAsunto(s)
Leucemia Linfoide/sangre , Leucemia/sangre , Linfocitos/citología , Antineoplásicos/farmacología , Nucléolo Celular , Núcleo Celular , Cromosomas , Técnicas de Cultivo , Diagnóstico Diferencial , Humanos , Leucemia/diagnóstico , Leucemia Linfoide/diagnóstico , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Microscopía Electrónica , Microscopía de Contraste de Fase , Prednisolona/farmacologíaAsunto(s)
Dimetilsulfóxido/farmacología , Leucemia Linfoide/patología , Linfocitos/efectos de los fármacos , Animales , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Calor , Humanos , Técnicas In Vitro , Leucemia/patología , Linfocitos/crecimiento & desarrollo , Linfoma/patología , Linfoma de Células B Grandes Difuso , Ratones , Neoplasias Experimentales/patología , Neutrófilos/efectos de los fármacos , Prednisolona/farmacología , Ratas , Bazo/citología , Timo/citologíaRESUMEN
Tests were make in this and in previous studies on the cytocidal action of cold (27 degrees), heat (43-50 degrees) anoxia, EDTA, colchicine and vincristine on non-dividing lymphocytes from normal individuals and from patients with chronic lymphocytic leukaemia. The reagents were selected for this work because they have been reported to have an effect on microtubules of various types of cells. All of the reagents were found to be more toxic to leukaemic than to normal lymphocytes. These findings are in accord with the hypothesis that vincristine produces a cytocidal effect by its action on the microtubules of leukaemic lymphocytes in interphase, that microtublues of leukaemic lymphocytes are more sensitive to reagents than those of normal lymphocytes, and that microtubules of leukaemic lymphocytes have abnormal cytopharmacological reactions.