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Int J Mol Sci ; 22(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34298882


Platelets can modulate cancer through budding of platelet microparticles (PMPs) that can transfer a plethora of bioactive molecules to cancer cells upon internalization. In acute myelogenous leukemia (AML) this can induce chemoresistance, partially through a decrease in cell activity. Here we investigated if the internalization of PMPs protected the monocytic AML cell line, THP-1, from apoptosis by decreasing the initial cellular damage inflicted by treatment with daunorubicin, or via direct modulation of the apoptotic response. We examined whether PMPs could protect against apoptosis after treatment with a selection of inducers, primarily associated with either the intrinsic or the extrinsic apoptotic pathway, and protection was restricted to the agents targeting intrinsic apoptosis. Furthermore, levels of daunorubicin-induced DNA damage, assessed by measuring gH2AX, were reduced in both 2N and 4N cells after PMP co-incubation. Measuring different BCL2-family proteins before and after treatment with daunorubicin revealed that PMPs downregulated the pro-apoptotic PUMA protein. Thus, our findings indicated that PMPs may protect AML cells against apoptosis by reducing DNA damage both dependent and independent of cell cycle phase, and via direct modulation of the intrinsic apoptotic pathway by downregulating PUMA. These findings further support the clinical relevance of platelets and PMPs in AML.

Apoptose/fisiologia , Micropartículas Derivadas de Células/fisiologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Daunorrubicina/farmacologia , Células THP-1/fisiologia , Apoptose/efeitos dos fármacos , Plaquetas , Micropartículas Derivadas de Células/efeitos dos fármacos , Micropartículas Derivadas de Células/metabolismo , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Células THP-1/efeitos dos fármacos , Células THP-1/metabolismo
Cancers (Basel) ; 13(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919720


The role of platelets in cancer development and progression is increasingly evident, and several platelet-cancer interactions have been discovered, including the uptake of platelet microparticles (PMPs) by cancer cells. PMPs inherit a myriad of proteins and small RNAs from the parental platelets, which in turn can be transferred to cancer cells following internalization. However, the exact effect this may have in acute myelogenous leukemia (AML) is unknown. In this study, we sought to investigate whether PMPs could transfer their contents to the THP-1 cell line and if this could change the biological behavior of the recipient cells. Using acridine orange stained PMPs, we demonstrated that PMPs were internalized by THP-1 cells, which resulted in increased levels of miR-125a, miR-125b, and miR-199. In addition, co-incubation with PMPs protected THP-1 and primary AML cells against daunorubicin-induced cell death. We also showed that PMPs impaired cell growth, partially inhibited cell cycle progression, decreased mitochondrial membrane potential, and induced differentiation toward macrophages in THP-1 cells. Our results suggest that this altering of cell phenotype, in combination with decrease in cell activity may offer resistance to daunorubicin-induced apoptosis, as serum starvation also yielded a lower frequency of dead and apoptotic cells when treated with daunorubicin.

Transfus Apher Sci ; 49(1): 90-4, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23791798


Blood doping in sports has been a hot topic of present. Longitudinal follow up of hematological parameters in different endurance sports, during the 1990s and early 2000s, has provided considerable suspicions about extensive blood manipulation, with performance enhancing effects. Recent doping revelations in the media also prove that blood doping is not an anticipated myth but it is, in fact, real. Erythropoiesis stimulating agents and autologous blood transfusions are used in synergy with substantial effect on the maximum oxygen uptake and delivery to muscles. Whilst both methods of blood manipulation represent a potential health hazard, in the context of an elevated hematocrit, nevertheless despite a number of suspicious deaths amongst athletes, this has not yet been fully documented. A reliable test for detection of recombinant human erythropoietin was implemented in 2000, but this is probably circumvented by microdose regimens. The Athlete's Biological Passport represents the progeny of the idea of an indirect approach based on long term monitoring of hematological parameters, thus making it possible to detect autologous blood doping and erythropoietin use after the substance is excreted. Nevertheless with advances in anti-doping measures it is possible that the levels of excretion of substances used can be masked. Clearly more sensitive and specific diagnostic tools and research/development in these areas of major concern are warranted, which, combined with changes in the athlete's attitude, will help in reaching the vision of fair play.

Transfusão de Sangue Autóloga/métodos , Doping nos Esportes/métodos , Transfusão de Sangue Autóloga/efeitos adversos , Transfusão de Sangue Autóloga/estatística & dados numéricos , Transfusão de Sangue Autóloga/tendências , Doping nos Esportes/estatística & dados numéricos , Doping nos Esportes/tendências , Humanos
Transfus Apher Sci ; 48(2): 277-81, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23465378


Anemia is a common comorbidity of lymphoproliferative malignancies, especially in multiple myeloma. Blood transfusions and ESAs (erythropoiesis stimulating agents) are both possible treatment options, but the latter is often preferred because of the potential risks of unwanted side effects related to blood transfusions. Evidence is accumulating that the use of ESAs in above clinical conditions is safe and effective and not associated with an increase in mortality or serious adverse events. 69.1% of patients achieved a hemoglobin response defined as an increase in hemoglobin of>2g/dl while receiving ESAs and concomitant chemotherapy. If supplemented with iron the hemoglobin response rate can be increased and hence the total dosage and financial cost reduced. A hemoglobin response is often accompanied by an increase in quality of life. HYPO% (hypochromic erythrocytes<5%) is believed to be both a significant positive predictor for the Hb response and also an indicator for iron supplementation if⩾5%. Conventional biochemical markers like serum ferritin concentration and transferrin saturation are not reliable for this use. The effect of EPO stimulating agents as the predictor of the Hb response, quality of life, mortality and the potential adverse events are discussed.

Anemia , Eritropoese/efeitos dos fármacos , Hematínicos/uso terapêutico , Neoplasias Hematológicas , Transtornos Linfoproliferativos , Anemia/sangue , Anemia/etiologia , Anemia/mortalidade , Anemia/patologia , Anemia/terapia , Transfusão de Sangue , Feminino , Ferritinas/sangue , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Hemoglobinas/metabolismo , Humanos , Ferro/sangue , Ferro/uso terapêutico , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Masculino , Qualidade de Vida
Transfusion ; 53 Suppl 1: 124S-130S, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23301964


The Blood Far Forward (BFF) research program was established to conduct blood product efficacy and safety studies, donor performance studies, and research on optimal training methods to improve the safety of blood collection and transfusion performed by Norwegian Naval Special Operation Commando soldiers. The use of intravenous fluids for volume replacement during hemorrhagic shock is controversial, but it is currently the standard of care. In the far-forward environment, large volume resuscitation for massive bleeding is a great challenge. Crystalloid and colloid solutions add weight and bulk to the medic's kit, require temperature sensitive storage, and should be warmed before infusion to prevent hypothermia. Excessive use of these solutions causes a dilutional coagulopathy, acidosis, and potentially increased inflammatory injury compared with blood products. Type-specific whole blood from an uninjured combat companion on the other hand is almost always available. It is warm, replaces intravascular volume, and provides oxygen delivery and hemostatic capacity to prevent or treat shock and coagulopathy. Whole blood may be ideal for the resuscitation of combat casualties with hemorrhagic shock. BFF program pilot studies on use of platelet-sparing leukoreduction filters, whole blood transport tolerance, donor performance, and autologous reinfusion of 24-hour ambient temperature stored whole blood have been performed and suggest the feasibility of expanding whole blood use in resuscitation. If successful, the BFF program will change tactics, techniques, and procedures with a new lifesaving capability.

Transfusão de Sangue/métodos , Hemorragia/terapia , Infusões Intravenosas/métodos , Medicina Militar/métodos , Militares/educação , Ressuscitação/métodos , Transfusão de Sangue/normas , Meio Ambiente , Hemorragia/etiologia , Humanos , Infusões Intravenosas/normas , Medicina Militar/educação , Medicina Militar/normas , Avaliação de Programas e Projetos de Saúde , Ressuscitação/educação , Ferimentos e Lesões/complicações