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1.
Anticancer Res ; 39(9): 5203-5207, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519634

RESUMO

BACKGROUND: A retrospective analysis was performed to investigate the survival outcomes in pediatric acute lymphoblastic leukemia (ALL) based on time period. We hypothesized that improvement has been obtained with the time-dependent therapeutic era and rise in the gross domestic product (GDP) and Human Development Index (HDI). MATERIALS AND METHODS: Data from 710 children who were treated for ALL between 1958 and 2018 at a single pediatric center were analyzed for probability of 5-year overall survival (pOS), event-free survival (pEFS) and relapse risk (pRR). Time periods were defined by the treatment protocols used in seven consecutive therapeutic eras. RESULTS: Over the 60-year period analyzed, pOS increased from 1.2% to 90.7%, pEFS from 1.2% to 86.6%, and pRR decreased from 98.8% to 9.9% for patients treated in the past decade. Risk of mortality for patients who received chemotherapy and hematopoietic cell transplant was reduced to 9.9% in the recent era, however, no statistically significant survival difference was found between patients treated with stem cell transplant and those not. CONCLUSION: The therapeutic era, related to improved GDP and HDI, was a statistically significant predictor of increased OS from ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Biomarcadores Tumorais , Biópsia , Criança , Pré-Escolar , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Avaliação de Resultados (Cuidados de Saúde) , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento
2.
Artigo em Inglês | MEDLINE | ID: mdl-31306338

RESUMO

High-dose chemotherapy with autologous hematopoietic stem cell transplantation improves event-free survival in patients with high-risk neuroblastoma. However, in heavily pretreated patients, poor marrow function can be an obstacle in the successful proceeding of therapy. Priming with plerixafor plus filgrastim is an option for effective mobilization and collection of stem cells. In addition, thrombopoietin agonist eltrombopag can improve the outcome of posttransplantation thrombocytopenia and poor graft function in the posttransplant setting. We describe a case of a child with high-risk neuroblastoma, for whom plerixafor and eltrombopag were used as an effective and safe supportive therapy.

3.
Ann Transplant ; 24: 374-382, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31235684

RESUMO

BACKGROUND The objective of this study was the analysis of transplant outcomes and survival in children treated with allogeneic hematopoietic cell transplantation (alloHCT) for non-malignant disorders, with a focus on risk factor analysis of transplant-related mortality (TRM). MATERIAL AND METHODS The treatment outcome was analyzed retrospectively in 10 consecutive years in 4 pediatric transplant centers in Poland. To compare the outcomes, patient data were analyzed according to the diagnosis, age at transplant, donor type, stem cell source, conditioning regimens, transplanted CD34+ cells dose, and pediatric TRM score. RESULTS From 183 analyzed patients, 27 (14.8%) died, all of them due to transplant-related complications. TRM occurred more frequently in matched unrelated donor (MUD) transplant recipients vs. matched sibling donor (MSD) transplant recipients (p=0.02); in peripheral blood (PB) recipients vs. bone marrow (BM) recipients (p=0.004); and in patients receiving >5×106/kg CD34+ cells (p<0.0001). OS differed significantly according to underlying disease comparing to other diagnoses. Lower survival was found in patients transplanted from MUD (p=0.02). OS was higher in patients receiving BM (p=0.001) and in those receiving ≤5×106/kg CD34+ cells (p<0.001). Multivariate analysis showed lower probability of TRM in BM recipients (p=0.04). The probability of TRM was higher in SCID patients (p=0.02) and in patients receiving >5×106/kg CD34+ cells (p=0.0001). CONCLUSIONS Underlying disease, stem cell source, and CD34+ dose higher than 5×106/kg were the most important risk factors for TRM, and they all affected OS.

4.
Anticancer Res ; 38(10): 6009-6013, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30275233

RESUMO

BACKGROUND/AIM: Immune recovery is a key factor in the management of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study analyzed the factors contributing to immune reconstitution after allo-HSCT. PATIENTS AND METHODS: Overall, 65 children with malignant or non-malignant diseases were included in multivariate analyses. RESULTS: The following factors contributed to a faster immune recovery: peripheral blood as a stem cell source and reactivation of CMV infection for CD3+ and CD4+ lymphocyte subpopulations; reactivation of CMV infection for CD8+ subset; donor EBV-IgG+ and no EBV reactivation for CD19 lymphocytes; recipient age below 10 years and peripheral blood as a stem cell source for NK cells. For CD2 and CD4/CD8 ratio no factor was significant in multivariate analysis. CONCLUSION: Patients receiving a graft from an EBV-IgG-positive donor and not having early EBV post-transplant viremia show faster recovery of the B-cells, while patients with early CMV-DNA-emia have a better re-establishment of T-cell subsets.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/imunologia , Infecções por Vírus Epstein-Barr/virologia , Neoplasias Hematológicas/imunologia , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4/imunologia , Subpopulações de Linfócitos/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Humanos , Lactente , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Subpopulações de Linfócitos/patologia , Subpopulações de Linfócitos/virologia , Masculino , Prognóstico , Transplante Homólogo , Ativação Viral
5.
Pediatr Transplant ; 22(3): e13158, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29396905

RESUMO

The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant-related reasons. The most frequently observed causes of TRM were toxic complications effecting with organ failure (38%), followed by infections (26%), PTLD (14.3%), and GvHD (16.7%). There was no statistical difference in the incidence of TRM depending on stem cell source (P = .209) and primary diagnosis (P = .301). According to TRM score, TRM was significantly higher in high-risk group (P = .006). High-risk patients had lower survival comparing to low/intermediate group (P = .0001). OS did not differ between ALL, AML, and MDS/JMML groups. The study confirmed the utility of factors included in TRM score stratification in assessing the risk of transplant procedure in pediatric patients transplanted for malignancies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicas/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Leucemia/mortalidade , Linfoma/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Adulto Jovem
6.
J Cell Biochem ; 118(1): 116-126, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27261372

RESUMO

The aim of the study was to extend the potential use of human stem cells isolated from amniotic fluid in medical applications by confirming their high homogeneity and quality. Amniotic fluid samples were collected during amniocentesis from 165 women during pregnancy. The proliferation rate, clonogenicity, karyotype, aging process, pluripotent cell markers, expression of surface markers, and the potential to differentiate into adipose, bone and cartilage cells of hAFSCs were analyzed. Obtained results revealed that mesenchymal stem cells could be derived successfully from amniotic fluid, which exhibit properties comparable with MSCs of other origins. It is the first study, in which such a large group of patients was involved. Comprehensive statistical and biological analysis were conducted some of which clearly being innovative in relation to human amniotic fluid-derived stem cells. J. Cell. Biochem. 118: 116-126, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Líquido Amniótico , Separação Celular/métodos , Células-Tronco Pluripotentes , Adolescente , Adulto , Líquido Amniótico/citologia , Líquido Amniótico/metabolismo , Antígenos de Diferenciação/biossíntese , Proliferação de Células/fisiologia , Separação Celular/normas , Senescência Celular/fisiologia , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Gravidez
7.
J Cell Biochem ; 118(5): 1097-1107, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27608167

RESUMO

The objective of this study was to evaluate complex biological properties of human stem cells isolated from adipose tissue (ASCs) harvested utilizing different methods: surgical resection (R), power-assisted liposuction (PAL), and laser-assisted liposuction (LAL). ASCs were isolated from healthy donors, due to surgical resection, power-, and laser-assisted liposuction. Isolated cells were characterized by their clonogenicity, proliferation rate, doubling time, multilineage differentiation, and senescence potential. The average number of ASCs from 1g/1 ml of solid adipose tissue/lipoaspirate was 2.9 × 105 ± 2.4 × 105 , 1.1 × 105 ± 0.8 × 105 , and 1.2 × 105 ± 0.7 × 105 , respectively, for ASCsR, ASCsPAL, and ASCsLAL. However, number of colonies formed by ASCsR and ASCsPAL was significantly higher compared to the average number of colonies formed by ASCsLAL. Also, in comparison to other analyzed cell groups, ASCsPAL obtained the highest proliferative activity. All analyzed cells were characterized by stable expression of CD90 and CD44 markers during prolonged culture. Expression of CD34 and CD45 markers was decreasing in subsequent passages. Presented study shows that different ASCs collection method affects some basic characteristics of these cells, such as number of isolated cells, clonogeneity, or doubling time. J. Cell. Biochem. 118: 1097-1107, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Adipócitos/citologia , Tecido Adiposo/cirurgia , Lipectomia/métodos , Manejo de Espécimes/métodos , Células-Tronco/citologia , Tecido Adiposo/citologia , Contagem de Células , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Feminino , Voluntários Saudáveis , Humanos
9.
Medicine (Baltimore) ; 94(52): e2369, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26717380

RESUMO

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. The chemotherapy for ALL is associated with a profound secondary immune deficiency.We evaluated the number and phenotype of natural killer (NK) cells at diagnosis, after the intensive chemotherapy and following the completion of the entire treatment for patients with ALL. The fraction, absolute number, and percentage of NK cells expressing interferon-γ were determined in full blood samples. The fraction of NK cells expressing CD158a, CD158b, perforin, A, B, and K granzymes was examined in isolated NK cells.We have shown that patients assessed at ALL diagnosis showed significantly lower values of the fraction of NK cells and percentage of NK cells with the granzyme A expression. Additionally, the absolute number of NK cells, the expression of CD158a, CD158b, perforin, and granzyme A were significantly lower in patients who completed intensive chemotherapy. Also, there was a significantly higher fraction of NK cells expressing granzyme K in patients who completed the therapy.Abnormalities of NK cells were found at all stages of the treatment; however, the most pronounced changes were found at the end of intensive chemotherapy.


Assuntos
Células Matadoras Naturais/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Granzimas/imunologia , Humanos , Lactente , Interferon gama/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Contagem de Linfócitos , Masculino , Perforina/imunologia , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Receptores KIR2DL1/imunologia , Receptores KIR2DL3/imunologia , Adulto Jovem
10.
Oncotarget ; 6(26): 22776-98, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26254295

RESUMO

In general, detection of peritoneal carcinomatosis (PC) occurs at the late stage when there is no treatment option. In the present study, we designed novel drug delivery systems that are functionalized with anti-CD133 antibodies. The C1, C2 and C3 complexes with cisplatin were introduced into nanotubes, either physically or chemically. The complexes were reacted with anti-CD133 antibody to form the labeled product of A0-o-CX-chem-CD133. Cytotoxicity screening of all the complexes was performed on CHO cells. Data showed that both C2 and C3 Pt-complexes are more cytotoxic than C1. Flow-cytometry analysis showed that nanotubes conjugated to CD133 antibody have the ability to target cells expressing the CD133 antigen which is responsible for the emergence of resistance to chemotherapy and disease recurrence. The shortest survival rate was observed in the control mice group (K3) where no hyperthermic intraperitoneal chemotherapy procedures were used. On the other hand, the longest median survival rate was observed in the group treated with A0-o-C1-chem-CD133. In summary, we designed a novel drug delivery system based on carbon nanotubes loaded with Pt-prodrugs and functionalized with anti-CD133 antibodies. Our data demonstrates the effectiveness of the new drug delivery system and provides a novel therapeutic modality in the treatment of melanoma.


Assuntos
Cisplatino/administração & dosagem , Cisplatino/química , Sistemas de Liberação de Medicamentos/métodos , Hipertermia Induzida/métodos , Nanotubos de Carbono/química , Neoplasias Peritoneais/terapia , Antígeno AC133 , Animais , Anticorpos/administração & dosagem , Anticorpos/química , Anticorpos/imunologia , Antígenos CD/química , Antígenos CD/imunologia , Terapia Combinada , Modelos Animais de Doenças , Glicoproteínas/química , Glicoproteínas/imunologia , Imunotoxinas/administração & dosagem , Imunotoxinas/química , Imunotoxinas/imunologia , Injeções Intraperitoneais , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/química , Peptídeos/imunologia , Neoplasias Peritoneais/tratamento farmacológico , Taxa de Sobrevida
11.
Pol Arch Med Wewn ; 125(3): 132-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25643927

RESUMO

INTRODUCTION: Left ventricular (LV) function and prognosis in patients after myocardial infarction are associated with some angiographic parameters. OBJECTIVES: The aim of the study was to assess the associations between the TIMI score in the infarct-related artery (IRA) before percutaneous coronary intervention (PCI), myocardial blush grade (MBG) following effective PCI, and the extent of collaterals measured using the Rentrop scale and plasma levels of vascular endothelial growth factor (VEGF) and angiogenin, number of CD34⁺ cells, as well as LV ejection fraction (LVEF) and wall motion score index (WMSI). PATIENTS AND METHODS: In 62 patients with the first ST-segment elevation myocardial infarction (STEMI) treated with PCI and bare metal stent implantation, plasma VEGF and angiogenin levels as well as the number of CD34⁺ cells were assessed before PCI, 24 hours after PCI, at discharge, and at 30 days following STEMI. LVEF and WMSI were evaluated by echocardiography at discharge and at 1 and 6 months after STEMI. RESULTS: Patients with TIMI 0-1 flow in the IRA before PCI (64.6% of the patients) had significantly higher troponin I and VEGF levels as well as a higher number of CD34⁺ cells than patients with TIMI 3 flow. Patients with TIMI 0-1 flow also had worse LV systolic function at 1 and 6 months following STEMI. Neither the MBG grade nor the Rentrop score showed associations with the mobilization of CD34⁺ cells, VEGF and angiogenin levels, and parameters of L V systolic function. CONCLUSIONS: Early patency of the IRA and lower myocardial necrosis seem to be more important for LV function assessed in patients 6 months after STEMI than mobilization of CD34⁺ cells and levels of angiogenic factors.


Assuntos
Antígenos CD34/metabolismo , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/cirurgia , Fator A de Crescimento do Endotélio Vascular/sangue , Angiografia Coronária , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Intervenção Coronária Percutânea , Prognóstico , Índice de Gravidade de Doença
12.
Mol Clin Oncol ; 3(1): 237-243, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25469302

RESUMO

Malignancy and oncologic treatment lead to various secondary immune disorders. In particular, little is known regarding immune reconstitution following cancer therapy. Lymphocytes, their subpopulations and immunoglobulin serum concentrations were assessed in patients with Hodgkin's disease at diagnosis (group I, 26 patients), cessation of therapy (group II, 21 patients) and 2 years after treatment (group III, 18 patients). Absolute lymphocyte count was significantly decreased in group II only (15/21 vs. 6/26 and 0/18 patients). In group I, the absolute count of the following subsets were decreased: Cluster of differentiation 19+ (CD19+) (18/26 patients), CD3+ (13/26), CD3+CD4+ (11/26) and CD3+CD8+ (7/26). In group II, the reduction of CD19+, CD3+ and CD3+CD4+ cell counts was evident (12/21, 16/21 and 19/21 patients, respectively), with the CD3+CD4+/CD3+CD8+ ratio distinctly lowered in the majority of patients (16/21). Similar changes in the percentages of lymphocyte subsets were observed. In the majority of patients in group III, the percentage of lymphocyte subsets were normal, but absolute lymphocyte counts were elevated (CD19+ in 11/18, CD3+ in 12/18, CD3+CD4+ in 13/18 and CD3+CD8+ in 11/18 patients). In half the patients at diagnosis, immunoglobulin G (IgG) was significantly elevated. In conclusion, disorders assessed in the percentage distribution and individual subpopulations of lymphocytes was applicable mainly to patients at the time of the diagnosis and shortly following completion of treatment. The analysis of time-distant consequences showed disorders only in the content of the percentage of CD4+ memory cells. The concentration of IgG at the time of diagnosis was significantly elevated in half the patients, which is possibly associated with the pathogenesis of the disease. The treatment does not appear to noticeably affect the production of IgG, IgA and IgM.

14.
Anticancer Res ; 34(12): 7379-82, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25503176

RESUMO

BACKGROUND: Keratinocyte growth factor (palifermin) is used for prevention of mucositis in adults following autologous and allogeneic hematopoietic stem cell transplantation (HSCT). It is known that palifermin decreases length of initial hospital stay, mean number of days of total parenteral nutrition (TPN) and the use of opioids for pain control in oral mucositis in adults. There are limited data evaluating palifermin use in children following autologous HSCT. AIM: The objective of the present study was the analysis of efficacy and safety of palifermin in children undergoing auto-HSCT. PATIENTS AND METHODS: This matched-pair analysis study included 62 pediatric patients undergoing first auto-HSCT receiving palifermin on a compassionate-use basis (study group, n=31) or not (control group, n=31). RESULTS: Palifermin decreased the incidence of severe (grade 3-4 WHO) oral mucositis (p=0.041), length of hospitalization (p=0.047) and contributed to the shorter duration of oral mucositis (p=0.035) and lower incidence of clinically or microbiologically documented infections (p=0.038). There were no differences between groups in opioid use, neutrophil and platelet recovery, TPN use and gastrointestinal hemorrhage. CONCLUSION: Palifermin decreases the incidence and severity of oral mucositis in children undergoing autologous HSCT.


Assuntos
Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estomatite/tratamento farmacológico , Estomatite/prevenção & controle , Adolescente , Autoenxertos , Criança , Feminino , Hospitalização , Humanos , Masculino , Análise por Pareamento
15.
PLoS One ; 9(8): e105295, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25162451

RESUMO

The purpose of this study was to compare: a new five-layered poly (L-lactide-co-caprolactone) (PLC) membrane and small intestinal submucosa (SIS) as a control in rat urinary bladder wall regeneration. The five-layered poly (L-lactide-co-caprolactone) membrane was prepared by an electrospinning process. Adipose tissue was harvested from five 8-week old male Wistar rats. Adipose derived stem cells (ADSCs) were seeded in a density of 3×10(6) cells/cm2 onto PLC membrane and SIS scaffolds, and cultured for 5-7 days in the stem cell culture medium. Twenty male Wistar rats were randomly divided into five equal groups. Augmentation cystoplasty was performed in a previously created dome defect. Groups: (I) PLC+ 3×10(6)ADSCs; (II) SIS+ 3×10(6)ADSCs; (III) PLC; (IV) SIS; (V) control. Cystography was performed after three months. The reconstructed urinary bladders were evaluated in H&E and Masson's trichrome staining. Regeneration of all components of the normal urinary bladder wall was observed in bladders augmented with cell-seeded SIS matrices. The urinary bladders augmented with SIS matrices without cells showed fibrosis and graft contraction. Bladder augmentation with the PLC membrane led to numerous undesirable events including: bladder wall perforation, fistula or diverticula formation, and incorporation of the reconstructed wall into the bladder lumen. The new five-layered poly (L-lactide-co-caprolactone) membrane possesses poorer potential for regenerating the urinary bladder wall compared with SIS scaffold.


Assuntos
Mucosa Intestinal/citologia , Poliésteres/química , Regeneração , Engenharia Tecidual/métodos , Tecidos Suporte , Bexiga Urinária/fisiologia , Adipócitos/citologia , Adipócitos/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Mucosa Intestinal/fisiologia , Masculino , Membranas Artificiais , Ratos , Ratos Wistar , Bexiga Urinária/cirurgia
16.
Arch Immunol Ther Exp (Warsz) ; 61(6): 483-93, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23974130

RESUMO

To evaluate the mesenchymal stem cells (MSCs) influence on cytokines and matrix metalloproteinases (MMPs) expression in rat bladder wall regeneration. MSCs cultures from the bone marrow were established. Acellular matrices from the bladder submucosa were prepared. Bladders were reconstructed using cell-seeded (n = 5) and unseeded (n = 5) grafts. MSCs were injected into the bladder wall (n = 5), bladders were incised and MSCs were injected into the circulation (n = 5) or were left intact (n = 5). Animals were killed after 3 months. Bladder histology and immunohistochemical staining of IL-2, IL-4, IL-6, IL-10, TNF-α, TGF-ß1, IFN-γ, MMP-2, and MMP-9 were done. Bladders reconstructed with cell-seeded grafts mimicked native tissue, while unseeded grafts revealed shrinkage and morphological irregularities. There were no morphological changes in bladders of other groups. Different pattern of cytokine and MMP expression was observed. Increased expression of anti-inflammatory cytokines and MMPs in bladder promotes detrusor regeneration.


Assuntos
Citocinas/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/fisiologia , Miócitos de Músculo Liso/fisiologia , Bexiga Urinária/fisiologia , Animais , Medula Óssea/patologia , Células Cultivadas , Regulação da Expressão Gênica , Masculino , Metaloproteinase 9 da Matriz/genética , Ratos , Ratos Endogâmicos BB , Regeneração , Transplante de Células-Tronco , Bexiga Urinária/lesões
17.
Kardiol Pol ; 71(5): 464-71, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23788086

RESUMO

BACKGROUND: Left ventricular (LV) systolic function is a significant prognostic factor in patients after myocardial infarction (MI). Multiple angiogenic and inflammatory factors are involved in postinfarction LV remodelling process. In addition, CD34+progenitor cells mobilised from bone marrow and tissue niches participate in regeneration of the infarcted myocardium. AIM: To examine relationships between LV ejection fraction (LVEF) and wall motion score index (WMSI) and the number of CD34+ cells and plasma levels of vascular endothelial growth factor (VEGF), angiogenin and such inflammatory factors as interleukin 6 (IL-6), interleukin 8 (IL-8), and high-sensitivity C-reactive protein (hsCRP) in patients with ST-elevation MI (STEMI). METHODS: The study group included 61 patients with STEMI treated with primary percutaneous coronary intervention (PCI)involving bare metal stent implantation. Plasma levels of the evaluated angiogenic and inflammatory factors were measured by flow cytometry at 4 time points (just before PCI, 24 h later, at hospital discharge, and 30 days after STEMI). LVEF and WMSI were measured by echocardiography at hospital discharge, 1 month later, and 6 months later. We compared angiogenic and inflammatory factor levels in patients with no improvement of the LV systolic function during the follow-up (group 1, n = 22)vs. those with improved LV systolic function (group 2, n = 39). RESULTS: No differences in the levels of VEGF, angiogenin, IL-6, IL-8, and hsCRP, and the number of CD34+ cells were observed between the two groups. Despite this, we found significant negative correlations between hsCRP level and LVEF,and positive correlations between hsCRP level and WMSI in both patient groups, but these correlations were much stronger in group 1. We also found a significant negative correlation between WMSI at 6 months and the number of CD34+ cells measured 24 h after PCI. CONCLUSIONS: 1. Evaluation of plasma VEGF, angiogenin, IL-6, IL-8, and hsCRP levels and the number of CD34+ cells at different time points in patients with STEMI did not allow predicting the direction of changes in LVEF and WMSI. 2. Observed significant correlations between hsCRP level and LVEF and WMSI may suggest a harmful effect of inflammation on postinfarction myocardial remodelling. 3. A significant negative correlation between the number of CD34+ and WMSI suggests that increased mobilisation of these cells might have a beneficial effect on systolic function after MI.


Assuntos
Antígenos CD34/metabolismo , Mobilização de Células-Tronco Hematopoéticas , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Proteína C-Reativa/metabolismo , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/metabolismo , Valor Preditivo dos Testes , Ribonuclease Pancreático/sangue , Volume Sistólico , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/sangue
18.
Acta Pol Pharm ; 70(1): 153-61, 2013 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23610971

RESUMO

With the object of improving the effectiveness of a malignant melanoma's treatment and a patients' quality of life, there is a serious need to identify new anticancer compounds, for example, among naturally derived compounds such as sodium butyrate. The aim of this study was to assess the combined impact of carboplatin (C) and sodium butyrate on the B16 melanoma viability by in vitro. B16 cell line was exposed to various concentrations of carboplatin (0.001-10 micromol/L) and sodium butyrate (1 to 100 mmol/L) for 24 h. LC10, LC50 and LC90 values were calculated. The influence of carboplatin and sodium butyrate on the cell cycle and apoptosis was assessed. Additionally, magnetic stem cell sorting was performed, positive melanoma CD133 cells were isolated and the effects of carboplatin and sodium butyrate on cell viability with heterogeneous population of melanoma cells (CD133+/CD133-) was compared. For carboplatin LC50 and LC90 were 1.2 micromol/L and 4.58 pmol/L, respectively. For sodium butyrate LC50 and LC90 were 65.73 mmol/L and 275.06 mmol/L. The value for LC10 could not be determined. Sodium butyrate at the highest concentration (100.0 mmol/L) resulted in only 57.36% mortality of cells. A synergistic effect of both compounds was observed in low concentrations of sodium butyrate and carboplatin. That synergism disappeared at concentrations corresponding to LC50. At the concentration corresponding to LC50 C and high concentration of sodium butyrate, a decrease of cell numbers in phase G2/M was observed (r = -0.97). Cells were arrested in phase G1/G0 and S. The presented results exclude the possibility of the combined application of sodium butyrate and carboplatin in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Butiratos/farmacologia , Carboplatina/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Melanoma Experimental/patologia , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Glicoproteínas/metabolismo , Separação Imunomagnética , Melanoma Experimental/imunologia , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Peptídeos/metabolismo , Fatores de Tempo
19.
Int J Urol ; 20(5): 537-42, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23088347

RESUMO

The aim of this study was to show that conditioned medium might induce transdifferentiation of hair follicle stem cells into urothelial-like cells. Several conditioned media and culture conditions (skeletal muscle cell conditioned medium, smooth muscle cell conditioned medium, fibroblast conditioned medium, transforming growth factor-conditioned medium, urothelial cell conditioned medium, and co-culture of hair follicle stem cells and urothelial cells) were used. The hair follicle stem cells phenotype from rat whisker hair follicles was checked by using flow cytometry and immunofluorescence. Cytokeratins 7, 8, 15 and 18 were used as markers. Urothelial cell conditioned medium increased the expression of urothelial markers (cytokeratin 7, cytokeratin 8, cytokeratin 18), whereas it decreased a hair follicle stem cells marker (cytokeratin 15) after 2 weeks of culture. This process depended on the time of cultivation. This medium was able to sustain the epithelial phenotype of the culture. Other media including a co-culture system failed to induce similar changes. Smooth muscle conditioned medium resulted in a loss of cells in culture. Hair follicle stem cells are capable of differentiating into urothelial-like cells in vitro when exposed to a bladder-specific microenvironment.


Assuntos
Células-Tronco Adultas/fisiologia , Técnicas de Cultura de Células , Transdiferenciação Celular , Folículo Piloso/citologia , Urotélio/citologia , Animais , Células Cultivadas , Fenótipo , Ratos , Ratos Wistar
20.
Leuk Lymphoma ; 54(6): 1256-62, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23088710

RESUMO

A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine. For patients with ALL, a combined five-drug ITRT profile for prednisolone, l-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for probability of disease-free survival (pDFS) in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For patients with AML, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can possibly be regarded as a risk factor in childhood acute leukemias.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Seguimentos , Humanos , Recém-Nascido , Prognóstico , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
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