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1.
Blood Adv ; 5(14): 2852-2862, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34283175

RESUMO

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.


Assuntos
Linfoma de Burkitt , Infecções por HIV , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/epidemiologia , Intervalo Livre de Doença , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Recidiva Local de Neoplasia , Rituximab , Reino Unido , Estados Unidos/epidemiologia
2.
Haematologica ; 106(7): 1932-1942, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538152

RESUMO

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.


Assuntos
Linfoma de Burkitt , Neoplasias do Sistema Nervoso Central , Infecções por HIV , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/epidemiologia , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/epidemiologia , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Rituximab/uso terapêutico , Adulto Jovem
3.
Blood ; 137(3): 374-386, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-32663292

RESUMO

We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.


Assuntos
Linfoma de Burkitt/sangue , Linfoma de Burkitt/tratamento farmacológico , Adulto , Idoso , Linfoma de Burkitt/genética , Feminino , Rearranjo Gênico/genética , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-myc/genética , Resultado do Tratamento , Estados Unidos
4.
Int J Mol Sci ; 21(3)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991762

RESUMO

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, thereby creating a need for new treatments to control hair loss and prevent balding. Human hair follicle dermal papilla cells (hDPCs), a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions like androgenic alopecia. This study aimed to evaluate the intensity-dependent effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on the expression of anagen-related molecules in hDPCs in vitro. We examined the effect of ELF-EMF on hDPCs to determine whether activation of the GSK-3ß/ERK/Akt signaling pathway improved hDPC activation and proliferation; hDPCs were exposed to ELF-EMFs at a frequency of 70 Hz and at intensities ranging from 5 to 100 G, over four days. Various PEMF intensities significantly increased the expression of anagen-related molecules, including collagen IV, laminin, ALP, and versican. In particular, an intensity of 10 G is most potent for promoting the proliferation of hDPC and expression of anagen-related molecules. Moreover, 10 G ELF-EMF significantly increased ß-catenin and Wnt3α expression and GSK-3ß/ERK/Akt phosphorylation. Our results confirmed that ELF-EMFs enhance hDPC activation and proliferation via the GSK-3ß/ERK/Akt signaling pathway, suggesting a potential treatment strategy for alopecia.


Assuntos
Campos Eletromagnéticos , Regulação da Expressão Gênica/efeitos da radiação , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos da radiação , Biomarcadores , Proliferação de Células , Células Cultivadas , Derme/citologia , MAP Quinases Reguladas por Sinal Extracelular , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Humanos , Fosforilação , Via de Sinalização Wnt/efeitos da radiação
5.
Biotechnol Prog ; 33(1): 201-211, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27790871

RESUMO

Biophysical wave stimulus has been used as an effective tool to promote cellular maturation and differentiation in the construction of engineered tissue. Pulsed electromagnetic fields (PEMFs) and sound waves have been selected as effective stimuli that can promote neural differentiation. The aim of this study was to investigate the synergistic effect of PEMFs and sound waves on the neural differentiation potential in vitro and in vivo using human bone marrow mesenchymal stem cells (hBM-MSCs). In vitro, neural-related genes in hBM-MSCs were accelerated by the combined exposure to both waves more than by individual exposure to PEMFs or sound waves. The combined wave also up-regulated the expression of neural and synaptic-related proteins in a three-dimensional (3-D) culture system through the phosphorylation of extracellular signal-related kinase. In a mouse model of photochemically induced ischemia, exposure to the combined wave reduced the infarction volume and improved post-injury behavioral activity. These results indicate that a combined stimulus of biophysical waves, PEMFs and sound can enhance and possibly affect the differentiation of MSCs into neural cells. Our study is meaningful for highlighting the potential of combined wave for neurogenic effects and providing new therapeutic approaches for neural cell therapy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:201-211, 2017.


Assuntos
Diferenciação Celular/efeitos da radiação , Células-Tronco Mesenquimais/efeitos da radiação , Células-Tronco Neurais/efeitos da radiação , Osteogênese/efeitos da radiação , Células da Medula Óssea/citologia , Proliferação de Células/efeitos da radiação , Campos Eletromagnéticos , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Humanos , Neurônios/citologia , Neurônios/efeitos da radiação , Som
6.
Biotechnol J ; 11(11): 1397-1404, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27440447

RESUMO

Various animal models of stroke have been developed to simulate the human stroke with the development of the ischemic method facilitates preclinical stroke research. The photothrombotic ischemia model, based on the intravascular photochemical reaction, is widely used for in vivo studies. However, this study has limitations, which generated a relatively small-sized infarction model on superficial cortex compared to that of the MCAO stroke model. In this study, the photothorombosis mouse model is adapted and the optimum conditions for generation of cell death and deficits with high reproducibility is determined. The extent of damage within the cortex was assessed by infarct volume and cellular/behavioral analyses. In this model, the neural cell death and inflammatory responses is detected; moreover, the degree of behavioral impairment is correlated with the brain infarct volume. Further, to enhance the understanding of neural repair, the effect of neural differentiation by transplantation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) is analyzed. The authors demonstrated that transplantation of BM-MSCs promoted the neural differentiation and behavioral performance in their photothrombosis model. Therefore, this research was meaningful to provide a stable animal model of stroke with low variability. Moreover, this model will facilitate development of novel MSC-based therapeutics for stroke.


Assuntos
Isquemia Encefálica/terapia , Trombose Intracraniana/terapia , Transplante de Células-Tronco Mesenquimais , Acidente Vascular Cerebral/terapia , Animais , Células da Medula Óssea/citologia , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Diferenciação Celular/genética , Modelos Animais de Doenças , Humanos , Trombose Intracraniana/genética , Trombose Intracraniana/patologia , Células-Tronco Mesenquimais , Camundongos , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/fisiopatologia , Volume Sistólico
7.
J Nanosci Nanotechnol ; 15(8): 5512-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26369110

RESUMO

Monodispersed magnetite (Fe3O4) nanoparticles (NPs) were prepared through the thermal decomposition method. The obtained NPs were surface modified with silica (SiO2) and polyethylene glycol (PEG), to enhance their stability in aqueous environment and their cellular uptake efficiency for biomedical applications. The NPs were characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FT-IR) spectroscopy, and dynamic light scattering (DLS). The cytotoxicity of these NPs on bone marrow mesenchymal stem cells (BM-MSCs) was measured by MTT assay (cell viability test) at various concentrations (2, 5, 12.5, 25, and 50 µg/mL). The cells remained more than 90% viable at concentrations as high as 50 µg/mL. To compare the cellular uptake efficiency, these NPs were treated in BM-MSCs and the Fe concentration within the cells was measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. The uptake process displayed a time- and dose-dependency. The uptake amount of SiO2-coated Fe3O4 (Fe3O4@SiO2) NPs was about 10 times higher than that of the PEG-coated ones (Fe3O4@PEG).


Assuntos
Materiais Revestidos Biocompatíveis/síntese química , Nanopartículas de Magnetita/química , Polietilenoglicóis/química , Dióxido de Silício/química , Células-Tronco/química , Células-Tronco/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Materiais Revestidos Biocompatíveis/toxicidade , Relação Dose-Resposta a Droga , Humanos , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Teste de Materiais , Tamanho da Partícula , Polietilenoglicóis/toxicidade , Dióxido de Silício/toxicidade , Células-Tronco/efeitos dos fármacos , Propriedades de Superfície
8.
Appl Biochem Biotechnol ; 174(4): 1233-1245, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25099373

RESUMO

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been investigated as a new cell-therapeutic solution due to their capacity that could differentiate into neural-like cells. Extremely low-frequency electromagnetic fields (ELF-EMFs) therapy has emerged as a novel technique, using mechanical stimulus to differentiate hBM-MSCs and significantly enhance neuronal differentiation to affect cellular and molecular reactions. Magnetic iron oxide (Fe3O4) nanoparticles (MNPs) have recently achieved widespread use for biomedical applications and polyethylene glycol (PEG)-labeled nanoparticles are used to increase their circulation time, aqueous solubility, biocompatibility, and nonspecific cellular uptake as well as to decrease immunogenicity. Many studies have used MNP-labeled cells for differentiation, but there have been no reports of MNP-labeled neural differentiation combined with EMFs. In this study, synthesized PEG-phospholipid encapsulated magnetite (Fe3O4) nanoparticles are used on hBM-MSCs to improve their intracellular uptake. The PEGylated nanoparticles were exposed to the cells under 50 Hz of EMFs to improve neural differentiation. First, we measured cell viability and intracellular iron content in hBM-MSCs after treatment with MNPs. Analysis was conducted by RT-PCR, and immunohistological analysis using neural cell type-specific genes and antibodies after exposure to 50 Hz electromagnetic fields. These results suggest that electromagnetic fields enhance neural differentiation in hBM-MSCs incorporated with MNPs and would be an effective method for differentiating neural cells.


Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Campos Eletromagnéticos , Nanopartículas de Magnetita , Células-Tronco Mesenquimais/metabolismo , Neurônios/metabolismo , Células da Medula Óssea/citologia , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Neurônios/citologia , Polietilenoglicóis/farmacologia , Solventes/farmacologia
9.
Biotechnol Appl Biochem ; 60(6): 596-602, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24033637

RESUMO

Transplanting mesenchymal stem cells into injured lesions is currently under study as a therapeutic approach for spinal cord injury. In this study, the effects of a pulsed electromagnetic field (PEMF) on injured rat spinal cord were investigated in magnetic nanoparticle (MNP)-incorporated human bone marrow-derived mesenchymal stem cells (hBM-MSCs). A histological analysis revealed significant differences in MNP-incorporated cell distribution near the injured site under the PEMF in comparison with that in the control group. We confirmed that MNP-incorporated cells were widely distributed in the lesions under PEMF. The results suggest that MNP-incorporated hBM-MSCs were guided by the PEMF near the injured site, and that PEMF exposure for 8 H per day over 4 weeks promoted behavioral recovery in spinal cord injured rats. The results show that rats with MNP-incorporated hBM-MSCs under a PEMF were more effective on the Basso, Beattie, and Bresnahan behavioral test and suggest that the PEMF enhanced the action of transplanted cells for recovery of the injured lesion.


Assuntos
Células da Medula Óssea/citologia , Campos Eletromagnéticos , Nanopartículas de Magnetita , Células-Tronco Mesenquimais/citologia , Traumatismos da Medula Espinal , Animais , Comportamento Animal , Humanos , Transplante de Células-Tronco Mesenquimais , Regeneração Nervosa , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/cirurgia
10.
Life Sci ; 91(9-10): 329-37, 2012 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-22884804

RESUMO

AIMS: Adipose tissue-derived stem cells (AT-MSCs) have been proposed as a new source for nervous tissue damage due to their capacity of neural differentiation potential including neurons, oligodendrocytes and astrocytes. Recently, many studies have demonstrated that sub-sonic vibration (SSV) is an effective cell differentiation method but there have been no studies on the effect of SSV about AT-MSC differentiation into neural-like cells in vitro. Therefore, we examined the effect of SSV on AT-MSCs to investigate the differentiation potential of neural-like cells. MAIN METHODS: We assessed the changes in AT-MSCs by SSV during 4 days at 10, 20, 30 and 40 Hz (1.0 V). After stimulation, they were analyzed by RT-PCR, Western blot and immunohistological analysis using neural cell type-specific genes and antibodies. Further, to confirm the neural differentiation, we investigated adipogenic genes for RT-PCR analysis. For a mechanism study, we analyzed activation levels in time course of ERK phosphorylation after SSV. KEY FINDINGS: After 4-day SSV exposure, we observed morphological changes of AT-MSCs. Further, SSV induced gene/protein levels of neural markers while inhibiting adipogenesis and they were mainly upregulated at 30 Hz. In addition, phosphorylated ERK level was increased in a time-dependent manner upon 30 Hz SSV for 6h. SIGNIFICANCE: These results demonstrated that SSV affects AT-MSCs differentiation potential and 30 Hz SSV affected neural differentiation on AT-MSCs.


Assuntos
Tecido Adiposo/metabolismo , Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/metabolismo , Neurônios/metabolismo , Vibração , Adipogenia/fisiologia , Tecido Adiposo/citologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosforilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Regulação para Cima/fisiologia
11.
Life Sci ; 90(15-16): 591-9, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22406078

RESUMO

AIMS: Adult stem cells, such as umbilical cord-derived mesenchymal stem cells (UC-MSCs), have the potential to differentiate into various types of cells, including neurons. Research has shown that mechanical stimulation induces a response in MSCs, specifically, low and high intensity sub-sonic vibration (SSV) has been shown to facilitate wound healing. In this study, the effects of SSV were examined by assessing the proliferation and differentiation properties of MSCs. MAIN METHODS: hUC-MSCs were isolated from Wharton's jelly, including the smooth muscle layer of the umbilical cord. During subculture, the cells were passaged every 5-6 days using nonhematopoietic stem cell media. To measure the effect of sonic vibration, SSV was applied to these cells continuously for 5 days. KEY FINDINGS: In this study, the morphology of hUC-MSCs was altered to resemble neurons by SSV. Further, the mRNA and protein levels of neuron-specific markers, including MAP2, NF-L, and NeuroD1, increased. In addition, other neural cell markers, such as GFAP and O4, were increased. These results suggest that hUC-MSCs differentiated into neural cells upon SSV nonselectively. In a mechanism study, the ERK level increased in a time-dependent manner upon SSV for 12 h. SIGNIFICANCE: The results of this study suggest that SSV caused hUC-MSCs to differentiate into neural cells via ERK activation.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/fisiologia , Neurônios/citologia , Cordão Umbilical/citologia , Vibração , Biomarcadores/metabolismo , Western Blotting , Primers do DNA/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Imuno-Histoquímica , Estimulação Física , Reação em Cadeia da Polimerase em Tempo Real , Geleia de Wharton/citologia
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