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1.
Leuk Lymphoma ; 37(5-6): 611-5, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-11042522
3.
Semin Hematol ; 34(1 Suppl 1): 67-72, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9122748

RESUMEN

Since the introduction of melphalan-prednisone for the treatment of multiple myeloma (MM) three decades ago, the prognosis of patients has not been improved by the addition of other agents, probably due to marked resistance of tumor cells, even at diagnosis, to commonly employed cytotoxic drugs. The biological basis for drug resistance is reviewed and current methods of diagnosis and staging delineated. The overview on treatment focuses on recurrent advances with myeloablative therapy demonstrating, in randomized and historically controlled trials, that high-dose therapy increases the incidence of true complete remission (CR) from 5% to approximately 40%, with an extension of median event-free (EFS) and overall (OS) survival durations to 3.5 and > or = 5 years, respectively. It is concluded that high-dose therapy should be offered to all patients with symptomatic meyloma, and current therapeutic research explores posttransplant immunotherapy.


Asunto(s)
Mieloma Múltiple/fisiopatología , Mieloma Múltiple/terapia , Antineoplásicos/uso terapéutico , Trasplante de Médula Ósea , Terapia Combinada , Humanos , Cariotipificación , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Cell Immunol ; 157(2): 462-77, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8069927

RESUMEN

The role of nitric oxide (NO) in the generation of lymphokine-activated killer (LAK) cells was investigated. Here we report that L-arginine analog NG-monomethyl-L-arginine (NMMA), a specific inhibitor of nitric oxide synthase, prevents LAK cell generation from cultured rat splenic cells. Accumulated NO endproduct nitrite (NO2-), as measured in the supernatants of rat splenic cells, correlated well with the generation of LAK cells. In contrast, cell proliferation induced by rIL-2 or by Con A was not affected by NMMA. Similarly, phenotypic expression of CD25 in rIL-2-stimulated cultures was unaffected. Furthermore, we could not observe differences in percentages of CD5-CD8+ cells (NK and LAK cell phenotype markers in rats) between rIL-2-stimulated cultures performed in the presence or absence of NMMA. LAK cell generation could no longer be blocked if NMMA was added to the rat cell cultures 24 hr after rIL-2 stimulation. To further confirm the role of NO in LAK cell generation, rat splenic cells were cultured in medium without L-arginine. Under such conditions rIL-2 could not induce LAK cell generation. Hemoglobin, which is a scavenger of NO, also inhibited LAK cell generation. Finally, addition of sodium nitroprusside (SNP) which releases NO in cultures was able to overcome blocking effects of NMMA. To attempt the identification of NO-producing cells, lysosomotropic agent, L-leucine methyl ester (LME), was used. Generation of LAK cell activity was virtually abolished in cell cultures treated with LME. Addition of SNP to cultures, however, sufficed to restore LAK cell generation. These results suggest that LAK cell precursors depend on a exogenous NO supply from other cell types in order to display their full cytotoxic potential. Similar results were also obtained by using mouse splenocytes as responder cells. In contrast, NMMA did not affect generation of LAK cells from human peripheral blood or spleen mononuclear cells.


Asunto(s)
Células Asesinas Activadas por Linfocinas/inmunología , Óxido Nítrico/fisiología , Animales , Arginina/análogos & derivados , Arginina/metabolismo , Arginina/farmacología , Células Cultivadas , Femenino , Hemoglobinas/farmacología , Humanos , Técnicas In Vitro , Leucina/análogos & derivados , Leucina/farmacología , Lisosomas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Endogámicas F344 , Factores de Tiempo , omega-N-Metilarginina
6.
Clin Nutr ; 13(1): 42-9, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16843351

RESUMEN

The role of glutamine (GLN) in the generation of lymphokine-activated killer (LAK) cell activity was investigated. LAK cells were derived from healthy donors and peripheral blood mononuclear cells (PBMC) were obtained using either unseparated PMBC or DR(-) CD3(-) CD16(+) CD56(+) enriched cells. PBMC were cultured for 6 or 10 days in medium supplemented with recombinant interleukin-2 (rlL-2; 100 U/ml) in the presence of different concentrations of GLN. K562 (natural killer-NK-sensitive targets), 1301 and U-937 (NK-resistant targets) cells were used as targets in the cytotoxic assays. Furthermore, the limiting dilution (LD) culture system was applied as an alternative to the bulk cell culture system. It was found that GLN affects the lytic potential of cultured cells while the frequency of responding cells did not significantly differ between the compared cell cultures performed in the presence of different amounts of GLN. Data on cell proliferation with IL-2 stimulation showed significant differences in cultures performed in the presence or absence of GLN. The results of present investigation suggest a supportive role of GLN in the generation of LAK cells. GLN deficit affects LAK cell killing activity by limiting the number of generated effector cells while acquisition of broad-range killing capacity was not affected.

7.
Lymphokine Cytokine Res ; 12(1): 21-4, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8457628

RESUMEN

Colostrum and blood samples were obtained on postpartum day 2 and 3 from 17 lactating, healthy women. After delipidation and molecular sieving fractionation of colostrum, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) could be readily measured by using a sensitive immunoassay. Antiviral activity could be also measured in some colostrum samples suggesting that interferon was biologically active. On the contrary, corresponding plasma samples showed negligible activity. These results expand previous data showing the presence of IL-1, tumor necrosis factor (TNF-alpha), and IL-6 in normal colostrum and are in line with the concept of a basal cytokine production in physiological conditions. All of these cytokines probably act on the oropharyngeal and gut-associated lymphoid tissue of the newborn and favor the development and maturation of the immune system.


Asunto(s)
Calostro/inmunología , Interferón gamma/metabolismo , Interleucina-6/metabolismo , Adulto , Femenino , Humanos , Sistema Inmunológico/crecimiento & desarrollo , Recién Nacido , Interferón gamma/sangre , Interleucina-6/sangre , Periodo Posparto/inmunología
8.
J Biol Regul Homeost Agents ; 5(4): 121-4, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1725087

RESUMEN

No one has ever doubted that maternal milk, in comparison to formula milk, has a far superior nutritional value. Colostrum has a well acknowledge crucial value for the survival of the animal species that cannot receive immunoglobulins through the placenta. Until recently the presence of cytokines in colostrum was unsuspected but it has been now clarified that normally there are at least four cytokines, namely interleukin 1 and 6, tumor necrosis factor and interferon gamma, that may exert an important immunostimulatory role particularly on the oropharyngeal-associated lymphoid tissue. As a corollary, physiological concentration of cytokines administered per os may exert a useful adjuvant activity in aged or immunodeficient people.


Asunto(s)
Calostro/fisiología , Citocinas/fisiología , Adulto , Calostro/química , Citocinas/análisis , Humanos , Interferones/farmacología , Tejido Linfoide/efectos de los fármacos
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