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2.
Nihon Shokakibyo Gakkai Zasshi ; 117(7): 626-634, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32655122

RESUMO

An 82-year-old male with a gallbladder mass was diagnosed with gallbladder carcinoma through various examinations. Cholecystectomy, gallbladder bed resection, and lymph node dissection were performed. The histological examination revealed a gallbladder adenosquamous carcinoma, and this tumor showed positive staining for granulocyte-colony stimulating factor (G-CSF). Recurrence of multiple liver metastases was detected on 25th day postoperatively. Unfortunately, the patient died on 97th day postoperatively. Here, we report a case of G-CSF-producing adenosquamous carcinoma of the gallbladder with rapid recurrence of liver metastases in the early postoperative period.


Assuntos
Carcinoma Adenoescamoso , Neoplasias da Vesícula Biliar , Neoplasias Hepáticas , Idoso de 80 Anos ou mais , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Humanos , Masculino , Recidiva Local de Neoplasia
3.
Gan To Kagaku Ryoho ; 47(5): 851-853, 2020 May.
Artigo em Japonês | MEDLINE | ID: mdl-32408335

RESUMO

BACKGROUND: Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor(G-CSF), has been used as prophylaxis for severe hematotoxicity induced by chemotherapy. We report a case of aortitis induced by pegfilgrastim administration during modified FOLFIRINOX(mFOLFIRINOX)chemotherapy for metastatic pancreatic cancer. CASE REPORT: A 65-year-old woman underwent a distal pancreatectomy for pancreatic tail cancer. Liver metastases appeared 2 years after the surgery. mFOLFIRINOX chemotherapy was started with prophylactic administration of pegfilgrastim. Eight days after the first administration and 6 days after administration of the 8th course, the patient developed a fever. The blood test results indicated severe inflammation. Computed tomography revealed a thickened aorta indicating aortitis. The symptoms rapidly improved with antibiotic therapy. We diagnosed aortitis induced by pegfilgrastim administration. CONCLUSION: Aortitis should be considered when a patient has unidentified inflammatory findings after receiving pegfilgrastim.


Assuntos
Aortite , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Aortite/induzido quimicamente , Feminino , Filgrastim , Granulócitos , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Polietilenoglicóis , Proteínas Recombinantes
5.
Bull Cancer ; 107(6): 629-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32387061

RESUMO

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Criança , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Síndrome de Down/epidemiologia , Interações Medicamentosas , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Risco , Medição de Risco , Terapia de Salvação , Avaliação de Sintomas
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 663-668, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319413

RESUMO

OBJECTIVE: To analyze the factors influencing the mobilization and collection of peripheral blood hematopoietic stem cells (HSC) in the patients with malignant hematological diseases. METHODS: The peripheral blood stem cells in 50 patients with hematological malignancies had been mobilized in the Hematology Department Zhongda Hospital. The factors, such as age, sex, mobilization regimen, disease status, cell separator were analyzed, and the effect of above-mentioned factors on stem cell mobilization was evaluated. And the correlation between WBC, Hb, Plt counts and CD34+ cell collection was anzlyzed. RESULTS: There was significant effect at mobilization regimen on the success rate and collection counts of CD34+ cells, while sex, age, interval between diagnosis and mobilization, previous chemotherapy regimen and bone marrow involvement showed no significant effect on stem cell collection. There was positively correlation of the WBC count, hemoglobin level of peripheral blood before apheresis with the collection of CD34+ cells . The WBC and MNC counts in peripheral blood before apheresis closely related with the success rate of mobilization. CONCLUSION: Chemotherapy plus combined with G-CSF mobilization regimens is superior to mobilization regimen of cytokine alone for collection of HSC. The WBC and MNC count in peripheral blood before apheresis can predict the optimal time for the PBSC collection and increase the success rate of mobilization and collection.


Assuntos
Remoção de Componentes Sanguíneos , Neoplasias Hematológicas , Mobilização de Células-Tronco Hematopoéticas , Antígenos CD34 , Fator Estimulador de Colônias de Granulócitos , Humanos , Contagem de Leucócitos
7.
Medicine (Baltimore) ; 99(15): e19746, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282735

RESUMO

RATIONALE: Toxic shock syndrome (TSS) typically is an acute onset multi-organ infection caused by TSS toxin-1 producing Staphylococcus aureus. Herein we describe a highly unusual case report. PATIENT CONCERNS: A male patient self-referred to the University of Minnesota Hospital with a chronic history of S aureus infection with accompanying fever, hypotension, and nonhealing, football-sized lesion on his leg. DIAGNOSIS: An unusual case presentation of TSS/hyperimmunoglobulin E syndrome is described. The patient had a leg wound from which TSS toxin-1 S aureus was isolated. The patient exhibited characteristic skewing of T cells to those with variable region, ß-chain T cell receptor-2. Other patients have been seen with related presentations. INTERVENTIONS: The following therapeutic regimen was instituted: vigorous antibacterial scrubs several times daily plus intravenous Ancef 3 days each month; intravenous infusions of immunoglobulin G infusions (28 gm) every 3 weeks; and weekly subcutaneous injections of recombinant granulocyte colony-stimulating factor. OUTCOME: Improvement was obvious within 3 months: no further cellulitic episodes occurred; the patient regained 95 pounds in 9 months; blanching and cyanosis of fingers disappeared within 3 months as did intractable pain although mild hypesthesias continued for 2 years; erythroderma resolved, and repeat skin biopsies performed after 2 years no longer demonstrated T cell receptor skewing. Although IgE levels have not completely returned to normal, the patient remains in excellent health. LESSONS: We propose that staphylococcal TSST-1 was responsible for the serious problems suffered by this patient as suggested by the following features: rapid onset of chronic, life-threatening, disorder that began with an episode of staphylococcal sepsis; the extraordinary elevation of IgE levels in this previously non-atopic individual; the acquired severe granulocyte chemotactic defect that accompanied this hyperimmunoglobulinemia ("Job Syndrome") with its accompanying wound-healing defect; and the striking diffuse erythroderma, including palmar erythema ("Red Man Syndrome") with hypotension and fever that also characterizes TSS.


Assuntos
Síndrome de Job/microbiologia , Choque Séptico/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Cefazolina/administração & dosagem , Cefazolina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/uso terapêutico , Infusões Intravenosas , Injeções Subcutâneas , Síndrome de Job/diagnóstico , Síndrome de Job/etiologia , Perna (Membro)/patologia , Masculino , Pessoa de Meia-Idade , Choque Séptico/diagnóstico , Choque Séptico/etiologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/patologia , Resultado do Tratamento , Ferimentos e Lesões/microbiologia
8.
PLoS One ; 15(3): e0228878, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134938

RESUMO

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.


Assuntos
Quimiocina CXCL12/genética , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Integrina alfa4beta1/genética , Polimorfismo de Nucleotídeo Único , Receptores CXCR4/genética , Molécula 1 de Adesão de Célula Vascular/genética , Adulto , Idoso , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Adulto Jovem
10.
PLoS One ; 15(3): e0230247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182268

RESUMO

Granulocyte-colony stimulating factor (G-CSF), a pleiotropic cytokine, belongs to the hematopoietic growth factor family. Recent studies have reported that G-CSF is a predictive biomarker of oocyte and embryo developmental competence in humans. The aim of our study was to determine whether CSF3 and its receptor (CSF3R) were expressed in porcine maternal reproductive tissues (oviduct and uterus), cumulus cells, and embryos and to investigate the effects of human recombinant G-CSF (hrG-CSF) supplementation during in vitro culture (IVC) on the developmental competence of pre-implantation embryos. To do this, we first performed reverse-transcription polymerase chain reaction (RT-PCR). Second, we performed parthenogenetic activation (PA), in vitro fertilization (IVF), and somatic cell nuclear transfer (SCNT) to evaluate the embryonic developmental potential after hrG-CSF supplementation based on various concentrations (0 ng/mL, 10 ng/mL, 50 ng/mL, and 100 ng/mL) and durations (Un-treated, Days 0-3, Days 4-7, and Days 0-7) of IVC. Finally, we examined transcriptional levels of several marker genes in blastocysts. The results of our study showed that CSF3 transcript was present in all samples we assessed. CSF3-R was also detected, except in cumulus cells and blastocysts from PA. Furthermore, 10 ng/mL and Days 0-7 were the optimal concentration and duration for the viability of in vitro embryonic development, especially for SCNT-derived embryos. The rate of blastocyst formation and the total cell number of blastocysts were significantly enhanced, while the number and index of apoptotic nuclei were significantly decreased in optimal condition groups compared to others. Moreover, the transcriptional levels of anti-apoptotis- (BCL2), proliferation- (PCNA), and pluripotency- (POU5F1) related genes were dramatically upregulated. In conclusion, for the first time, we demonstrated that CSF3 and CSF3R were expressed in porcine reproductive organs, cells, and embryos. Additionally, we determined that hrG-CSF treatment improved porcine embryonic development capacity in vitro.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Proteínas Recombinantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Blastocisto/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células do Cúmulo/efeitos dos fármacos , Técnicas de Cultura Embrionária/métodos , Feminino , Fertilização In Vitro/métodos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Técnicas de Transferência Nuclear , Oócitos/efeitos dos fármacos , Gravidez , Suínos
12.
Animal ; 14(S1): s44-s54, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32024567

RESUMO

Aspects of neutrophil function are diminished or dysregulated in dairy cows in the weeks just before and after calving, which appears to be an important contributor to the occurrence of retained placenta, mastitis, metritis and endometritis. The timing and mechanisms by which specific elements of neutrophil function are impaired are only partially understood. Oxidative burst capacity is the element of neutrophil function most consistently shown to be impaired in the week after calving, but that observation may partially be biased because oxidative burst has been studied more than other functions. There is sufficient evidence to conclude that the availability of calcium and glucose, and exposure to elevated concentrations of non-esterified fatty acids or ß-hydroxybutyrate affect some aspects of neutrophil function. However, these factors have mostly been studied in isolation and their effects are not consistent. Social stressors such as a competitive environment for feeding or lying space should plausibly impair innate immune function, but when studied under controlled conditions such effects have generally not been produced. Similarly, treatment with recombinant bovine granulocyte colony-stimulating factor consistently produces large increases in circulating neutrophil count with modest improvements in function, but this does not consistently reduce the incidence of clinical diseases thought to be importantly attributable to impaired innate immunity. Research is now needed that considers the interactions among known and putative risk factors for impaired neutrophil function in dairy cows in the transition period.


Assuntos
Doenças dos Bovinos/imunologia , Endometrite/veterinária , Imunidade Inata , Mastite Bovina/imunologia , Placenta Retida/veterinária , Ácido 3-Hidroxibutírico/metabolismo , Adaptação Fisiológica , Animais , Bovinos , Endometrite/imunologia , Metabolismo Energético , Ácidos Graxos não Esterificados/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos , Hipocalcemia , Lactação , Contagem de Leucócitos , Neutrófilos/metabolismo , Período Periparto , Placenta Retida/imunologia , Gravidez , Proteínas Recombinantes
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 275-282, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027289

RESUMO

OBJECTIVE: To investigate the effect of prostaglandin E2 recoptor 4 antagonist (EP4A) on the self-renewal ability of human CD34+ cells and its mechamism. METHODS: The peripheral blood hematopoietic stem cell of 20 healthy donors received the G-CSF-mobilization were collected, then the human CD34+ cells were sorted out by MACS microbead kit. The human CD34+ cells were treated with DMSO (control group), EP4A (EP4A group) and EP4A+EP4A antagonist (EP4A+EP4A group) for 72 hours. The differential genes and pathways related with CD34+ cell stemness were detected by Thermogram and Pathway enrichment analysis. and then the expression levels of protein and gene (ß-catenin, Nanog, Oct4, Sox2, Stat3, AKT, P38) were detected by qRT-PCR and Western blot respectively. RESULTS: EP4A could elevate the mRNA and protein expression of ß-catenin, Nanog, Oct4, Sox2, in comparison with control group, however, mRNA and protein expression of STAT3, AKT, P38 were not changed. When human CD34+ cell were cultured with EP4A+XAV939 it was found that the mRNA and protein expression of ß-catenin was downregulated, moreover the mRNA and protein expression of Nanog, Oct4, Sox2 were reduced. CONCLUSION: EP4A can upregulate stemness factors-ß-catenin, Nanog, Oct4 and Sox2 in human CD34+ cell in vitro, but not STAT3, AKT and P38.


Assuntos
Receptores de Prostaglandina E Subtipo EP4/metabolismo , Antígenos CD34 , Movimento Celular , Fator Estimulador de Colônias de Granulócitos , Humanos , Proteína Homeobox Nanog , Fator 3 de Transcrição de Octâmero , Prostaglandinas , RNA Mensageiro , Linfócitos T
14.
PLoS One ; 15(1): e0227449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004354

RESUMO

The SOD3 variant, SOD3R213G, results from substitution of arginine to glycine at amino acid 213 (R213G) in its heparin binding domain (HBD) and is a common genetic variant, reported to be associated with ischemic heart disease. However, little is understood about the role of SOD3R213G in innate immune function, and how it leads to dysfunction of the cardiovascular system. We observed pathologic changes in SOD3R213G transgenic (Tg) mice, including cystic medial degeneration of the aorta, heart inflammation, and increased circulating and organ infiltrating neutrophils. Interestingly, SOD3R213G altered the profile of SOD3 interacting proteins in neutrophils in response to G-CSF. Unexpectedly, we found that G-CSF mediated tyrosine phosphatase, SH-PTP1 was down-regulated in the neutrophils of SOD3R213G overexpressing mice. These effects were recovered by reconstitution with Wt SOD3 expressing bone marrow cells. Overall, our study reveals that SOD3R213G plays a crucial role in the function of the cardiovascular system by controlling innate immune response and signaling. These results suggest that reconstitution with SOD3 expressing bone marrow cells may be a therapeutic strategy to treat SOD3R213G mediated diseases.


Assuntos
Infiltração de Neutrófilos/fisiologia , Neutrófilos/metabolismo , Superóxido Dismutase/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , Miocárdio/metabolismo , Miocárdio/patologia , Neutrófilos/citologia , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética
15.
Ann Hematol ; 99(4): 819-828, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32025840

RESUMO

Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 106/kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Adulto , Antifúngicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Terapia Combinada , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Neutropenia Febril/induzido quimicamente , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Pré-Medicação , Intervalo Livre de Progressão , Estudos Prospectivos , Indução de Remissão , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Adulto Jovem
16.
Arch Oral Biol ; 112: 104668, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32032909

RESUMO

OBJECTIVE: The aim of this study was to evaluate the levels of Interleukin-1α (IL-1α), Interleukin-1ß (IL-1ß), Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-10 (IL-10), Interleukin-13 (IL-13), Vascular endothelial growth factor (VEGF), Granulocyte-colony stimulating factor (G-CSF), and Growth related oncogene (GRO) in the peri-miniscrew implant crevicular fluid (MICF) under orthodontic loading. DESIGN: The study sample comprised 14 miniscrews immediately loaded and 17 unloaded ones. A load of 200gF was immediately applied to the miniscrews in the loaded group after the placement surgery. Peri-miniscrew implant crevicular fluid was collected at baseline, at day 7, and at day 21. The levels of the biomarkers were measured using a multiplexed bead immunoassay. Intergroup comparisons were made using Mann-Whitney test. Friedman and Dunn's multiple comparison tests were used to evaluate intragroup differences over time. RESULTS: Although no statistical differences were observed between the groups at any time point for any of the 8 biomarkers evaluated, there was a statistically significant increase (p < 0.02) in the levels of all the biomarkers over time on both groups. CONCLUSIONS: An immediate loading of 200gF does not alter the balance in the inflammatory response in peri-miniscrew tissues.


Assuntos
Parafusos Ósseos , Interleucinas/metabolismo , Procedimentos de Ancoragem Ortodôntica , Adolescente , Adulto , Biomarcadores/metabolismo , Quimiocina CXCL1/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Inflamação , Masculino , Técnicas de Movimentação Dentária , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
17.
Exp Hematol ; 82: 33-42, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32045657

RESUMO

The erythroblastic island (EBI) is a multicellular structure forming an erythropoietic niche consisting of a central macrophage surrounded by a rosette of maturing erythroblasts. Since their discovery more than 60 years ago, simultaneous quantification and visualization of EBIs remain difficult. Although flow cytometry enables high-throughput quantification of cell aggregates co-expressing macrophage and erythroblast markers, it cannot visually confirm whether the aggregates are genuine EBIs. While immunofluorescence microscopy allows visualization of EBIs, its low throughput limits its use for quantification. In the current study we employed nine-channel imaging flow cytometry (IFC) to develop a method to directly visualize and quantify EBIs in the mouse bone marrow. We found that EBI central macrophages do express F4/80, VCAM-1, and CD169, but not CD11b or Ly6G, and that CD11b+Ly6G+F4/80- granulocytes are found associated at the periphery of 40%-60% EBIs. Furthermore, we show for the first time using IFC that in vivo treatment with the hematopoietic stem cell-mobilizing cytokine granulocyte colony-stimulating factor (G-CSF) reduced EBI frequency in the bone marrow by more than 100-fold. These results indicate that mobilizing doses of G-CSF cause a collapse of EBIs in the bone marrow.


Assuntos
Medula Óssea/metabolismo , Eritroblastos , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Granulócitos , Macrófagos , Animais , Antígenos de Diferenciação/biossíntese , Eritroblastos/citologia , Eritroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Granulócitos/citologia , Granulócitos/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos
19.
Cancer Immunol Immunother ; 69(2): 199-213, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31982939

RESUMO

Neutrophils play a major role in tumor biology. Among other functions, neutrophils can release extracellular traps (NETs), mesh-like structures of decondensed chromatin fibers, in a process termed NETosis. Originally characterized as an antimicrobial mechanism, NETosis has been described in cancer, but cancer-related predisposition is not clear. In the current study, we investigated the predisposition of circulating neutrophils to release NETs in lung cancer and the impact of G-CSF on this function, comparing circulating neutrophils isolated from cancer patients to the LLC and AB12 mouse models. We find that neutrophils from both healthy donors and cancer patients display high NETotic potential, with 30-60% of cells undergoing NETosis upon PMA stimulation. In contrast, neutrophils isolated from tumor-bearing mice displayed only 4-5% NETotic cells, though significantly higher than naive controls (1-2%). Despite differential mechanisms of activation described, Ionomycin and PMA mainly triggered suicidal rather than vital NETosis. G-CSF secreting tumors did not increase NETotic rates in murine neutrophils, and direct G-CSF stimulation did not promote their NET release. In contrast, human neutrophils strongly responded to G-CSF stimulation resulting also in a higher response to PMA + G-CSF stimulation. Our data show clear differences in NETotic potentials between human and murine neutrophils. We do not find a predisposition of neutrophils to release NETs in lung cancer patients compared to healthy controls, whereas cancer may modulate neutrophils' NETotic potential in mice. G-CSF secreted from tumors differentially affects murine and human NETosis in cancer. These important differences should be considered in future studies of NETosis in cancer.


Assuntos
Armadilhas Extracelulares/fisiologia , Neoplasias Pulmonares/imunologia , Neutrófilos/fisiologia , Animais , Linhagem Celular Tumoral , Armadilhas Extracelulares/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Ionomicina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Acetato de Tetradecanoilforbol/farmacologia
20.
Br J Radiol ; 93(1109): 20190147, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971824

RESUMO

Concerns have been raised about potential toxic interactions when colony-stimulating factors (CSFs) and chemoradiation are concurrently performed. In 2006, the ASCO guidelines advised against their concomitant use. Nevertheless, with the development of modern radiotherapy techniques and supportive care, the therapeutic index of combined chemotherapy, radiotherapy, and CSFs is worth reassessing. Recent clinical trials testing chemoradiation in lung cancer let investigators free to decide the use of concomitant CSFs or not. No abnormal infield event was reported after the use of modern radiotherapy techniques and concomitant chemotherapy regimens. These elements call for further investigation to set new recommendations in favour of the association of chemoradiation and CSFs. Moreover, radiotherapy could induce anticancer systemic effects mediated by the immune system in vitro and in vivo. With combined CSFs, this effect was reinforced in preclinical and clinical trials introducing innovative radioimmunotherapy models. So far, the association of radiation with CSFs has not been combined with immunotherapy. However, it might play a major role in triggering an immune response against cancer cells, leading to abscopal effects. The present article reassesses the therapeutic index of the combination CSFs-chemoradiation through an updated review on its safety and efficacy. It also provides a special focus on radioimmunotherapy.


Assuntos
Quimiorradioterapia/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Animais , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/terapia , Camundongos , Radioimunoterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Pequenas Células do Pulmão/terapia
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