Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
1.
J Exp Med ; 184(4): 1377-84, 1996 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8879210

RESUMO

Autonomous release of hematopoietic growth factors may play a crucial role in the pathogenesis of certain hematological malignancies. Because of its cytokine synthesis-inhibiting action, interleukin 10 (IL-10) could be a potentially useful molecule to affect leukemic cell growth in such disorders. Chronic myelomonocytic leukemia (CMML) cells spontaneously form myeloid colonies (colony-forming units-granulocyte/macrophage) in methylcellulose, suggesting an autocrine growth factor-mediated mechanism. We studied the effect of recombinant human IL-10 (rhIL-10) on the in vitro growth of mononuclear cells obtained from peripheral blood or bone marrow of patients with CMML. IL-10 specifically binding to leukemic cells had a profound and dose-dependent inhibitory effect on autonomous in vitro growth of CMML cells. IL-10 significantly inhibited the spontaneous growth of myeloid colonies in methylcellulose in 10/11 patients, and autonomous CMML cell growth in suspension in 5/5 patients tested. Spontaneous colony growth from CMML cells was also markedly reduced by addition of antigranulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies, but not by addition of antibodies against G-CSF, IL-3, or IL-6, IL-10-induced suppression of CMML cell growth was reversed by the addition of exogenous GM-CSF and correlated with a substantial decrease in GM-CSF production by leukemic cells, both at the mRNA and protein levels. Our data indicate that IL-10 profoundly inhibits the autonomous growth of CMML cells in vitro most likely through suppression of endogenous GM-CSF release. This observation suggests therapeutic evaluation of rhIL-10 in patients with CMML.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Inibidores do Crescimento/farmacologia , Interleucina-10/farmacologia , Leucemia Mielomonocítica Crônica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Leucemia Mielomonocítica Crônica/patologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , RNA Mensageiro/análise , RNA Neoplásico/análise , Proteínas Recombinantes/farmacologia , Células-Tronco , Células Tumorais Cultivadas
2.
Leuk Lymphoma ; 39(3-4): 355-64, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11342316

RESUMO

Administration of interleukin-2 (IL-2) to cancer patients has been shown to transiently decrease the number of circulating hematopoietic progenitor cells, but the mechanism of this phenomenon is unknown. Recently, the interaction of vascular adhesion molecule-1 (VCAM-1) with leukocyte very late antigen-4 (VLA-4) has been demonstrated to play a crucial role in the adhesion of progenitor cells to bone marrow stromal elements. Cytokine induced upregulation of VCAM-1 leads to increased binding of progenitor cells to stromal cells in vitro, and inhibition of this interaction by monoclonal antibodies is associated with marked progenitor cell mobilisation in vivo. In the present study we serially determined peripheral blood progenitor cell numbers during IL-2 treatment (10 courses) in 6 cancer patients and determined in parallel levels of soluble VCAM-1 as a surrogate marker for the in vivo activation of this molecule. Our data indicate that continuous intravenous administration of IL-2 for 5 days leads to a marked decrease of circulating progenitor cells associated with a substantial increase of circulating VCAM-1. Circulating myeloid progenitor cells (CFU-GM) dropped from a mean value of 167 +/- 187 / ml pre IL-2 to 16 +/- 15 / ml on day 3 (p < 0.01). Similarily, mean erythroid progenitors (BFU-E) decreased from 282 +/- 204 / ml before IL-2 administration to 86 +/- 61 / ml on day 3 (p < 0.005). In contrast, soluble VCAM-1 rose from a mean value of 1814 +/- 451 ng/ml before to 4607 +/- 736 ng/ml at the end of IL-2 therapy (p < 0.0001). Sera from IL-2 treated patients did not inhibit hematopoietic colony formation from normal bone marrow. These results suggest redistribution and increased adhesion of progenitor cells to stromal and/or endothelial elements during IL-2 via the VCAM-1/VLA-4 interaction as a possible mechanism for the decrease of circulating progenitor cells during IL-2 therapy.


Assuntos
Células-Tronco Hematopoéticas/efeitos dos fármacos , Interleucina-2/administração & dosagem , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos , Adulto , Idoso , Células Sanguíneas/citologia , Células Sanguíneas/imunologia , Células da Medula Óssea/efeitos dos fármacos , Adesão Celular , Feminino , Humanos , Imunoterapia , Injeções Intravenosas , Interleucina-2/farmacologia , Cinética , Masculino , Pessoa de Meia-Idade , Solubilidade , Molécula 1 de Adesão de Célula Vascular/fisiologia
3.
Acta Haematol ; 73(1): 1-5, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-3923760

RESUMO

15 patients with aplastic anemia were prospectively followed after having measurements of myeloid progenitor cells in bone marrow and blood. Treatment included androgens, low or high dose steroids and standardized supportive care. The median length of survival was 5.8 months. When patients were grouped according to the numbers of myeloid progenitor cells present in their blood and bone marrow, we found that the survival length of aplastic patients with higher progenitor cell numbers was prolonged when compared to that of patients with lower numbers of these cells. The prognostic information obtained from such in vitro cultures was particularly indicative when the patients were grouped according to 'growth' and 'no growth': the absence of colony-forming myeloid stem cells was associated with survival times significantly shorter than those of patients whose cells maintained their colony-forming capacity. Besides initial numbers of myeloid progenitor cells, only initial numbers of granulocytes were related to survival length. Thus, the measurement of myeloid progenitor cells in bone marrow and blood can be of prognostic value in patients with aplastic anemia.


Assuntos
Anemia Aplástica/patologia , Medula Óssea/patologia , Células-Tronco Hematopoéticas/patologia , Idoso , Anemia Aplástica/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
4.
Ann Hematol ; 83(1): 9-13, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-13680175

RESUMO

We have originally shown that spontaneous granulocyte/macrophage colony (CFU-GM) formation in semisolid medium is a characteristic in vitro feature of chronic myelomonocytic leukemia (CMML). However, the clinical significance of spontaneous CFU-GM growth in CMML is unknown so far. CFU-GM growth characteristics were studied in semisolid cultures in the absence of exogenous cytokines using peripheral blood mononuclear cells in 30 patients with CMML at first presentation. The median number of CFU-GM/10(5) MNC of all patients was 48.5 (range 0-622) with 18 patients having colony numbers below 100 (low CFU-GM growth) and 12 patients above 100 (high CFU-GM growth). Kaplan-Meier analysis revealed that patients with high CFU-GM growth had a significantly shorter survival than patients with low CFU-GM growth (median 6.5 vs. 44.5 months, p<0.00002). The probability of survival after 2 years was 60.5% for patients with low colony growth but 0% in those with high colony formation. Patients with CFU-GM >100 had a significantly higher WBC count, a higher LDH, and a higher number of blast cells in blood and bone marrow than patients with low colony growth. Moreover, patients with high colony growth had more often splenomegaly and lower platelet counts. In seven patients, in whom semisolid in vitro cultures were performed after transformation into RAEBT/AML, spontaneous colony growth was significantly increased as compared to CFU-GM growth in patients before transformation (median number/10(5) MNC 533, range 212-4553, p<0.005). This study demonstrates that high (>100) spontaneous CFU-GM formation in CMML at presentation correlates with increased disease activity and represents a novel and important prognostic factor predicting for short survival of CMML patients.


Assuntos
Granulócitos/patologia , Leucemia Mielomonocítica Crônica/patologia , Macrófagos/patologia , Células-Tronco Neoplásicas/patologia , Idoso , Idoso de 80 Anos ou mais , Ensaio de Unidades Formadoras de Colônias , Feminino , Humanos , Leucemia Mielomonocítica Crônica/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Risco , Análise de Sobrevida
5.
Blood ; 92(6): 1967-72, 1998 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-9731054

RESUMO

In polycythemia vera (PV) erythroid colonies that grow in vitro in the absence of exogenous erythropoietin (EPO) arise from the abnormal clone that is responsible for overproduction of red blood cells. Although the mechanism of autonomous formation of burst-forming units-erythroid (BFU-E) is not fully understood, a spontaneous release of growth regulatory molecules by PV cells and/or by accessory cells is likely to be involved. Because of its cytokine synthesis inhibiting action, interleukin-10 (IL-10) could be a potentially useful molecule to modulate abnormal erythropoiesis in PV. We studied the effect of recombinant human IL-10 on the EPO-independent growth of erythroid bursts derived from peripheral blood mononuclear cells (PBMNCs) of patients with PV. IL-10 showed a profound, dose-dependent, and specific inhibitory effect on autonomous BFU-E formation. Ten nanograms per milliliter of IL-10 significantly suppressed spontaneous growth of erythroid colonies in methylcellulose in five of five PV patients tested with a mean inhibition by 81% (range, 72-94). To elucidate the possible mechanism of the inhibitory action of IL-10 we further studied the effect of anticytokine antibodies on autonomous BFU-E growth and the ability of exogenous cytokines to restore IL-10-induced suppression of erythroid colony growth. Among a panel of growth regulatory factors tested (granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-3, granulocyte colony-stimulating factor, stem cell factor, and insulin-like growth factor-1) GM-CSF was the only molecule for which both an inhibition of spontaneous BFU-E formation by its respective antibody as well as a significant restimulation of erythroid colonies in IL-10-treated cultures by exogenous addition was found. Moreover, inhibition of GM-CSF production by IL-10 was shown in PV PBMNCs at the mRNA level. Our data indicate that autonomous BFU-E growth in PV can be profoundly inhibited by IL-10 and that this inhibitory effect seems to be at least in part secondary to suppression of endogenous GM-CSF production.


Assuntos
Células Precursoras Eritroides/efeitos dos fármacos , Eritropoetina/fisiologia , Inibidores do Crescimento/farmacologia , Interleucina-10/farmacologia , Policitemia Vera/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Divisão Celular/efeitos dos fármacos , Células Precursoras Eritroides/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Substâncias de Crescimento/farmacologia , Humanos , Soros Imunes/farmacologia , Interleucina-10/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade
6.
Scand J Haematol ; 26(4): 345-50, 1981 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6461059

RESUMO

Suppressor cells for colony forming cells (CFUC) were found in the bone marrow of 1 of 6 patients with aplastic anaemia. The assay applied was based on the fact that coexisting suppressor cells are more sensitive to dilution than CFUC, as long as adequate stimulation is provided by a source of colony stimulating activity. In the patient with suppressor cells, a 4 d trial of 1000 mg methylprednisolone per d failed to improve the blood cell production and had to be discontinued due to gastric irritation.


Assuntos
Anemia Aplástica/patologia , Medula Óssea/patologia , Células-Tronco Hematopoéticas/patologia , Linfócitos T Reguladores , Idoso , Anemia Aplástica/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Ann Hematol ; 69(6): 325-7, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7527662

RESUMO

Dyskeratosis congenita (DC) is a rare congenital X-linked disorder. The major clinical manifestations are abnormal skin pigmentation, nail dystrophy, and leukoplakia of mucosal membranes. About 50% of the patients develop bone marrow failure, which is partly responsible for the poor prognosis. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has been administered to some neutropenic patients with DC, but only a moderate stimulation of neutropoiesis has been observed. We report on a patient with DC treated with recombinant human granulocyte-colony-stimulating factor (rhG-CSF). This treatment resulted in a substantial dose-dependent increase in the neutrophil count.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hematopoese/efeitos dos fármacos , Neutropenia/tratamento farmacológico , Adulto , Humanos , Leucoplasia/complicações , Masculino , Unhas Malformadas , Transtornos da Pigmentação/tratamento farmacológico , Síndrome , Cromossomo X
8.
Br J Haematol ; 102(2): 535-43, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9695971

RESUMO

By participating in a randomized safety and efficacy study of pegylated-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) post induction and consolidation chemotherapy for de novo acute myeloid leukaemia, serial determinations of circulating haemopoietic progenitor cells were performed during 18 chemotherapy courses in eight patients (three receiving placebo; one, 2.5; and four, 5.0 microg/kg/d MGDF, respectively). Whereas failure to achieve complete remission (CR) was generally associated with poor progenitor cell increments following chemotherapy, substantial progenitor cell mobilization consistently occurred during haemopoietic recovery in patients entering, or in CR, with significantly higher peak values in patients receiving 5 microg/kg/d of MGDF as compared to controls. The median increases of progenitor cell numbers by chemotherapy alone and chemotherapy plus 5.0 microg/kg/d MGDF over that in normal individuals with steady-state haemopoiesis were 10- and 45-fold for CFU-GM, 3- and 17-fold for BFU-E, and 2- and 18-fold for CFU-mix. CFU-Mk levels were not increased above normal by chemotherapy alone but were 15-fold enhanced by chemotherapy plus MGDF. Recruitment of CD34+ cells post chemotherapy was also potentiated by MGDF. Our results suggest MGDF as a potent agent to augment progenitor cell mobilization after successful induction or consolidation chemotherapy in patients with AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Leucemia Mieloide/tratamento farmacológico , Trombopoetina/uso terapêutico , Doença Aguda , Adulto , Idoso , Método Duplo-Cego , Eritropoese/efeitos dos fármacos , Feminino , Hematopoese/efeitos dos fármacos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas
9.
Br J Haematol ; 113(1): 120-5, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11328291

RESUMO

We have analysed the results of semi-solid bone marrow cultures in 296 patients with de novo acute myeloblastic leukaemia (AML) and correlated them with the leukaemic karyotype. A favourable prognostic karyotype was found in 52 patients (group A, 18.3%), an intermediate karyotype in 163 patients (group B, 57.4%), and unfavourable cytogenetics were observed in 69 patients (group C, 24.3%). Median colony growth according to the three risk groups was 2 (range 0--344) in group A, 14.5 (range 0--5000) in group B and 50.0 (0--3000) in group C (A vs. B, P < 0.001; A vs. C, P < 0.001; B vs. C, P < 0.01). Among the patients treated with chemotherapy (n = 257), median colony growth was 10 (range 0-5000) in those who achieved complete remission (CR) compared with 56.5 (range 0-1000) in patients without remission (NR) (P = 0.002). The median colony growth of all patients [13/10(5) bone marrow mononuclear cells (BMMCs); range 0--5000] significantly discriminated between patients regarding survival (OS 11 vs. 7 months, P = 0.044). However, multiple Cox regression analysis revealed cytogenetic risk groups as the most important predictor for achieving CR, disease-free and overall survival, with colony growth adding no additional prognostic information. In 64 patients, colony growth was also investigated without the addition of exogenous cytokines. Interestingly, none of the patients with a favourable karyotype exhibited autonomous growth, whereas 50% with an intermediate and 73% of patients with an unfavourable karyotype displayed either partial or full autonomous growth in vitro (P = 0.0004). Our data suggest that the growth potential of the leukaemic clone seems to be critically influenced by the molecular changes emerging from chromosomal abnormalities.


Assuntos
Células da Medula Óssea/patologia , Aberrações Cromossômicas , Transtornos Cromossômicos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Divisão Celular , Análise Citogenética , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Fatores de Risco
10.
Vox Sang ; 81(3): 167-71, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11703859

RESUMO

BACKGROUND AND OBJECTIVES: Platelet count, thrombopoetin (TPO) level and the compartment of megakaryocyte progenitor cells (CFU-Mk) are major determinants in the regulation of thrombopoiesis. The aim of this study was to investigate the potential changes in the compartment of CFU-Mk and their correlation with serum TPO levels and platelet count after plateletpheresis. MATERIALS AND METHODS: Twelve healthy individuals were randomly assigned to undergo single-donor plateletpheresis. A collagen-based in vitro culture system was used to determine the number of peripheral blood (PB) CFU-Mk before and after donation and on days 1, 4 and 7 thereafter. TPO levels were measured by a specific enzyme-linked immunosorbent assay and whole blood counts were performed using an automated cell counter. RESULTS: The pre-apheresis platelet count (mean +/- SEM: 276 +/- 13 x 10(9)/l) decreased after plateletpheresis to a nadir of 194 +/- 8 x 10(9)/l (P < 0.001), showed a gradual increase on days 1 and 4, and reached pre-apheresis values by day 7 (280 +/- 11). The serum TPO levels were found to be significantly increased on days 1 and 7 as compared to baseline levels (baseline value 103.3 +/- 18.5 pg/ml versus day-1 value 135.8 +/- 25.8 pg/ml and day-7 value 132 +/- 30.19 pg/ml; P < 0.03 and P < 0.03, respectively). The numbers of CFU-Mk in PB were significantly elevated on day 4 only (125 +/- 21 colonies/ml of PB versus pre-apheresis values of 68 +/- 18 colonies/ml of PB, P < 0.005). CONCLUSIONS: These findings suggest that platelet loss during plateletpheresis affects thrombopoiesis at the progenitor cell level, probably through alterations in TPO plasma concentrations.


Assuntos
Megacariócitos/citologia , Células Progenitoras Mieloides/citologia , Plaquetoferese/instrumentação , Contagem de Células Sanguíneas , Técnicas de Cultura de Células/métodos , Hematopoese , Humanos , Cinética , Contagem de Plaquetas/instrumentação , Trombopoetina/sangue
11.
Blood ; 95(9): 2983-9, 2000 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-10779449

RESUMO

A recent study in dogs suggested that erythropoietin (EPO) not only promotes the synthesis of increased numbers of reticulated platelets but that these newly produced platelets are hyperreactive compared with controls. Because of the increasing use of EPO in the perioperative setting, we characterized the effects of EPO on platelet reactivity in healthy human volunteers. In a randomized, controlled trial, we studied the effects of EPO on platelet reactivity, thrombopoiesis, and endothelial activation in circumstances similar to those of autologous blood donation. Thirty healthy male volunteers received placebo or EPO (100 or 500 U/kg of body weight given intravenously) three times a week for 2 weeks and underwent phlebotomy on days 8 and 15. Thrombin receptor-activating peptide induced expression of P-selectin, and CD63 increased 2- to 3-fold during EPO treatment. The enhanced platelet reactivity was also reflected by a 50% increase in soluble P-selectin in plasma. Plasma E-selectin levels increased in a dose-dependent fashion by more than 100% during EPO treatment, indicating substantial activation of endothelial cells. A 10% to 20% increase in platelet counts was observed in both EPO groups on day 5. In the placebo group, platelets increased only several days after the first phlebotomy. The increase in platelet counts was not reflected by changes in the amounts of reticulated platelets or circulating progenitor cells. In summary, we found that EPO markedly enhances endothelial activation and platelet reactivity, which may adversely affect patients at cardiovascular risk. However, the increased platelet reactivity could be exploited in patients with platelet dysfunction. (Blood. 2000;95:2983-2989)


Assuntos
Plaquetas/fisiologia , Eritropoetina/farmacologia , Hematopoese/fisiologia , Adulto , Animais , Antígenos CD/análise , Plaquetas/efeitos dos fármacos , Moléculas de Adesão Celular/sangue , Cães , Método Duplo-Cego , Selectina E/sangue , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Eritropoetina/administração & dosagem , Eritropoetina/sangue , Hematopoese/efeitos dos fármacos , Hemoglobinas/metabolismo , Humanos , Infusões Intravenosas , Masculino , Oligopeptídeos/farmacologia , Selectina-P/sangue , Placebos , Contagem de Plaquetas/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/análise , Receptores de Trombina/fisiologia , Contagem de Reticulócitos/efeitos dos fármacos , Tetraspanina 30 , Fatores de Tempo
12.
J Immunol ; 151(8): 4221-7, 1993 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-7691941

RESUMO

Mast cells (MC3) belong to the hemopoietic system and arise from hemopoietic precursor cells. Human MC progenitors can be detected in the bone marrow as well as in the peripheral blood (pb) and are responsive to the mast cell growth factor SCF, the ligand of the c-kit tyrosine kinase receptor. However, little is known about the subsets of cells that become committed to and differentiate into mature human MC. In this study, the identity of the circulating MC progenitor, previously felt to be a monocyte (Mo) or basophil (Ba), was investigated. For this purpose, CD14+ pb monocytes, CD17+ pb basophils and CD34+ cord blood cells were purified to homogeneity (> 95%) from mononuclear cells (normal adult donors, n = 17, cord blood, n = 2) by counter-flow centrifugation followed by cell sorting with mAb. In the presence of rhSCF, MC developed in long term suspension culture from pure CD34+ cells but not from pure Mo, pure Ba, or Ly (MC-tryptase levels on day 42: CD14+ Mo: 3.7 +/- 0.8 vs CD17+ Ba: 3.2 +/- 0.5 vs Ly: 2.0 +/- 1.5 vs control: 196.5 +/- 92.5 ng/ml, p < 0.001). Depletion of CD34+ cells from MNC resulted in a loss of MC in long term suspension culture, whereas depletion of either Mo, Ba, or Ly did not. In methyl-cellulose cultures in the presence of rhSCF, MC and tryptase could be detected in pure (CFU-mast) and mixed (CFU-myeloid/mast) MC colonies. Together, MC do not originate from circulating Mo, Ba, or Ly. The circulating MC progenitor is a CD34+, c-kit+, Ly-, CD14-, CD17- colony-forming cell. This is the first definitive demonstration that mast cells are replenished directly from early hemopoietic progenitors and thus form a unique cell lineage within the hemopoietic system.


Assuntos
Antígenos CD/análise , Fatores de Crescimento de Células Hematopoéticas/farmacologia , Células-Tronco Hematopoéticas/fisiologia , Mastócitos/fisiologia , Monócitos/fisiologia , Antígenos CD34 , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos Ly/análise , Diferenciação Celular , Células Cultivadas , Feminino , Células-Tronco Hematopoéticas/imunologia , Humanos , Receptores de Lipopolissacarídeos , Masculino , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-kit , Receptores Proteína Tirosina Quinases/análise , Receptores de Fator Estimulador de Colônias/análise , Proteínas Recombinantes/farmacologia , Fator de Células-Tronco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA