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1.
J Clin Pharm Ther ; 47(12): 2115-2129, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36053969

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Chronic myeloid leukaemia (CML) microenvironment is responsible for resistance of leukaemic cells to tyrosine kinase inhibitor, altered adhesion, increased proliferation and leukaemic cells growth and survival through the secretion of many soluble molecules. We aimed at monitoring soluble L-selectin (sCD62L) and secreted protein acidic and rich in cysteine (SPARC) levels in chronic phase chronic myeloid leukaemia (CP-CML) patients and assessing the impact of imatinib on these parameters. METHODS: This prospective controlled clinical trial enrolled 35 subjects classified into two groups: control group included 10 healthy volunteers and CP-CML patients group included 25 newly diagnosed CP-CML patients received imatinib 400 mg once daily. sCD62L plasma levels, SPARC serum levels, breakpoint cluster region-Abelson1 (BCR-ABL1) %, complete blood count with differential, liver and kidney functions parameters were assessed at baseline and after 3 and 6 months of treatment. RESULTS AND DISCUSSION: At baseline, sCD62L and SPARC were significantly elevated in CP-CML patients (p < 0.05) compared to control group. After 3 months of treatment, sCD62L was non-significantly decreased (p > 0.05), while surprisingly SPARC was significantly increased (p < 0.05) compared to baseline. Moreover, after 6 months of treatment, sCD62L was significantly decreased (p < 0.05) and SPARC was non-significantly decreased (p > 0.05) compared to baseline. In addition, sCD62L was significantly correlated with WBCs and neutrophils counts, while SPARC was significantly correlated with lymphocytes count at baseline and after 3 and 6 months of imatinib treatment. WHAT IS NEW AND CONCLUSION: The elevated levels of sCD62L and SPARC at diagnosis in CP-CML patients could reflect their roles in CML pathogenesis and the dynamic changes in their levels during imatinib therapy might suppose additional mechanisms of action of imatinib beside inhibition of BCR-ABL. Furthermore, imatinib showed a significant impact on sCD62L and SPARC levels during treatment period.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Osteonectina/uso terapêutico , Estudos Prospectivos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Microambiente Tumoral
2.
Cytometry B Clin Cytom ; 96(2): 149-157, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30729673

RESUMO

BACKGROUND: Adhesion receptors have important role in cellular invasiveness and L-selectin is a primary determinant in the binding of chronic lymphocytic leukemia (CLL) cells to several glycated proteins on endothelial cells. We investigated L-selectin expression on CLL cells and explored the mechanisms that lead to their shedding. METHODS: Surface and soluble L-selectin expression levels were studied by flow cytometry and immunoassay, respectively. Magnetically isolated B-cells from patients and controls were investigated for total and protein phosphatase-2A activities. Flow cytometry of permeabilized cells was utilized for the determination of phosphorylated mitogen-activated protein kinase (pp38MAPK) and surface tumor necrosis factor alpha-converting enzyme expression (TACE). RESULTS: In CLL patients elevated absolute lymphocyte cell counts, high soluble and low surface L-selectin expression were observed. Similarly, TACE surface expression was significantly lower on B-CLL cells compared to normal B-cells. Both total phosphatase and protein phosphatase-2A activities were also significantly lower in B-CLL cells compared to normal B-cells and we found a consequently higher level of pp38 MAPK in B-CLL cells. Based on in vitro experiments a MAPK inhibitor could attenuate the phosphatase inhibitor's effect on L-selectin shedding. CONCLUSIONS: The lower phosphatase activity detectable in chronic lymphocytic leukemia, results in a downstream signaling cascade with subsequent reduction of surface L-selectin expression and this effect is mediated by enhanced phosphorylation of p38MAPK and an altered TACE expression. © 2019 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.


Assuntos
Selectina L/biossíntese , Leucemia Linfocítica Crônica de Células B/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Citometria de Fluxo , Humanos , Imunoensaio , Selectina L/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/diagnóstico , Contagem de Linfócitos , Monoéster Fosfórico Hidrolases/sangue
3.
Clin Rheumatol ; 35(12): 3063-3067, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27620619

RESUMO

In present study, we aimed to study salivary soluble L-selectin (sL-selectin), interleukin-7(IjL-7), and lymphotoxin-α levels in primary Sjögren's syndrome (pSS) and their clinical as well as serological correlations. pSS patients fulfilling either the American European Consensus Group (AECG) and/or the American college of Rheumatology (ACR) criteria were recruited. Age- and sex-matched hospital staff were recruited as healthy controls. Unstimulated saliva was collected by the spitting method; sL-selectin, IL-7, and lymphotoxin-α were measured in the saliva using commercial ELISA kits. Forty-three patients with pSS and 31 healthy controls were included in the study. Increased levels of sL-selectin and IL-7 were found in the saliva of patients as compared to controls. Lymphotoxin-α was undetectable in the saliva of pSS patients and controls. Salivary sL-selectin positively correlated with rheumatoid factor (r = 0.47; p < 0.003). No other variable including ESSDAI was significantly associated with salivary sL-selectin and IL-7 levels. Indian patients with primary Sjögren's syndrome have higher salivary sL-selectin and IL-7 levels than healthy controls.


Assuntos
Interleucina-7/química , Selectina L/química , Saliva/química , Síndrome de Sjogren/metabolismo , Adolescente , Adulto , Autoanticorpos/química , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia , Linfotoxina-alfa/química , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
J Clin Lab Anal ; 29(3): 191-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24798295

RESUMO

BACKGROUND: We sought to determine the association of plasma level of soluble L-selectin (sL-selectin) and F206L polymorphism of L-selectin with asthma. METHODS: A total of 90 asthmatic patients and 90 sex- and age-matched healthy controls were enrolled. The plasma level of sL-selectin was measured by enzyme-linked immunosorbent assay (ELISA) method. An amplification refractory mutation system polymerase chain reaction was performed to detect F206L polymorphism of L-selectin. RESULTS: The mean plasma levels of sL-selectin was significantly higher in the patients with asthma than the controls (2113 ± 466 vs. 1664 ± 322 ng/ml, P = 0.001). Logistic regression analysis after adjustment for age, sex, and body mass index demonstrated that plasma levels of sL-selectin are an independent biomarkers for asthma (odds ratio [OR], 1.86; 95% confidence interval [95% CI], 1.42-2.24). The area under the receiver operating characteristic (ROC) curve for sL-selectin was 0.792, 95% CI (0.732-0.862), P = 0.0001. Individuals with the minor homozygote of F206L polymorphism of L-selectin demonstrated a higher level of sL-selectin than the major homozygous (2319 ± 732 vs. 1917 ± 453 ng/ml, P = 0.02). No association was found between F206L polymorphism of L-selectin with asthma. CONCLUSION: Our study suggests that plasma level of sL-selectin is an independent biomarker for asthma.


Assuntos
Asma/sangue , Biomarcadores/sangue , Selectina L/sangue , Adulto , Asma/genética , Feminino , Genótipo , Humanos , Selectina L/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-638917

RESUMO

Objective To observe the changes of soluble L-selectin(sL-selectin) concentrations in children with viral encephalitis(VE) and probe its significance in pathogenesy and clinic.Methods Selecting 30 children with VE,including 14 mild case and 16 severe case.Collecting their venous blood and cerebrospinal fluid(CSF) in acute and recovery stage.Using double antibody sandwich enzyme-linked immunosorbent assay(ELISA) method to measure sL-selectin concentrations of serum and CSF and comparing with control group,respectively.Results SL-selectin concentrations from serum and CSF in the acute stage were significantly higher than those of control group(all P0.05).Conclusions L-selectin may participate in the pathologic course in VE.The concentrations of sL-selectin from serum and CSF are related with the patients′ condition and it has important reference value in judging patients′ condition,assessing their prognose and guiding clinical treatment.

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