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1.
Ren Fail ; 46(1): 2356708, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38803220

RESUMO

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median -12.12%, interquartile ranges (IQRs) -18.62 to -5.626) and creatine (median -46.91 µmol/L, IQR -64.70 to -29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03-25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.


Assuntos
Injúria Renal Aguda , Bortezomib , Taxa de Filtração Glomerular , Mieloma Múltiplo , Plasmaferese , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/etiologia , Plasmaferese/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Estudo de Prova de Conceito , Albumina Sérica Humana/análise , Albumina Sérica Humana/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Adulto , Terapia Combinada , Proteínas do Mieloma
2.
Curr Drug Deliv ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38424427

RESUMO

BACKGROUND: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 µg mL-1. CONCLUSION: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

3.
Clin Transl Oncol ; 25(10): 2983-2990, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37081223

RESUMO

PURPOSE: To investigate the value of red blood cell parameters in Myelodysplastic syndrome (MDS) diagnosis and their relations to MDS subtypes and risk groups. METHODS: The red blood cell parameter [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] levels [203 MDS, 99 aplastic anemia (AA), 145 megaloblastic anemia (MA)] were collected from a single-center retrospective cohort. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of the four parameters were calculated from the ROC. Furthermore, Kruskal-Wallis test and Dunn's Test were performed to determine erythrocyte parameters in different subtypes and prognostic risks MDS. RESULTS: There are significant statistic differences in RDW (P < 0.001), MCH (P = 0.036) and MCHC (P < 0.001) (MDS vs AA); RDW (P = 0.009), MCV (P < 0.001), MCH (P < 0.001) and MCHC (P = 0.001) (MDS vs MA); MCV (P = 0.011) and MCH (P = 0.008) (higher-risk MDS vs lower-risk MDS). Between MDS and MA, the area under the receiver operating characteristic curve (ROC) curve (AUC) values of MCV, MCH, MCHC, RDW were 0.846, 0.855, 0.617, and 0.593. Between MDS and AA, the AUC values of MCH, MCHC, RDW were 0.609, 0.671, and 0.662, respectively. CONCLUSIONS: The red blood cell parameters contribute to the differential diagnosis of MDS, AA and MA and are related to MDS subtypes and risk groups.


Assuntos
Eritrócitos , Síndromes Mielodisplásicas , Humanos , Estudos Retrospectivos , Índices de Eritrócitos , Síndromes Mielodisplásicas/diagnóstico , Prognóstico
4.
Cancer Control ; 30: 10732748231163648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895113

RESUMO

INTRODUCTION: Classical Philadelphia-negative myeloproliferative neoplasm (MPN) includes Essential Thrombocythemia (ET), Polycythemia Vera (PV) and Primary Myelofibrosis (PMF). The JAK2V617F mutation is part of the major criteria for diagnosis of MPN. WT1 is reported to be highly overexpressed in most hematological malignancy. Our aim was to explore the combination value of JAK2V617F allele burden and WT1 expression in distinguishing the subtype of MPN patients. METHODS: Allele specific real-time quantitative fluorescence PCR (AS-qPCR) was conducted to detect JAK2V617F allele burden. WT1 expression was assessed by RQ-PCR. Our study is a retrospective study. RESULTS: JAK2V617F allele burden and WT1 expression were different in MPN subgroups. The expression of WT1 in PMF and PV is higher than in ET. JAK2V617F allele burden in PMF and PV is also higher than in ET. ROC analysis indicated that combination of JAK2V617F allele burden and WT1 expression to discriminate ET and PV, ET and PMF, PV and PMF is 0.956, 0.871, 0.737 respectively. Furthermore, their ability to distinguish ET patients with high Hb levels from PV patients with high platelet counts is 0.891. CONCLUSIONS: Our data revealed that combination of JAK2V617F allele burden and WT1 expression is useful in distinguishing the subtype of MPN patients.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Humanos , Alelos , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Proteínas WT1/genética
5.
Colloids Surf B Biointerfaces ; 224: 113201, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36822117

RESUMO

Combination therapy is an effective way to alleviate the shortcoming of monotherapy and enhances therapeutic efficacy. Herein, a distinctive hollow mesoporous silica nanoparticle (HMSNs) encapsulated with folic acid-modified bovine serum albumin (BSA-FA), denoted as HBF, was engineered for tumor targeting and dual-responsive release of loaded-therapeutic agents MD (methylene blue (MB) and doxorubicin (DOX)). The BSA molecule as a ''gatekeeper'' prevents premature drug leakage and actively unloads the cargos through BSA detachment in response to intracellular glutathione (GSH). Folic acid (FA) promotes the specific intracellular delivery of the drug to folate receptor (FR)-expressing cancer cells to improve the efficacy of chemo-photodynamic therapy (PDT). In vitro drug release profiles showed that the drug carrier could achieve pH/redox-responsive drug release from MD@HBF owing to the cleavage of the imine bonds between HMSNs-CHO and BSA-FA and BSA intramolecular disulfide bond. Additionally, a series of biological evaluations, such as cell uptake experiments, toxicity experiments, and in vivo therapeutic assays indicated that MD@HBF possesses the features of accurately targeting FR-expressing 4T1 cells to induce cells apoptosis in vitro, exhibits outstanding tumor cell synergistic killing efficiency of chemo-photodynamic therapy (combination index CI = 0.325), and inhibits tumors growth. These results demonstrated that the strategy of combining HMSNs with stimuli-responsive biodegradable protein molecules could provide a new potential direction toward the ''on-demand'' drug release for precision chemo-photodynamic therapy in cancer treatment.


Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Dióxido de Silício/química , Soroalbumina Bovina/química , Doxorrubicina/química , Nanopartículas/química , Ácido Fólico , Sistemas de Liberação de Medicamentos/métodos , Porosidade , Liberação Controlada de Fármacos
6.
Eur J Med Chem ; 247: 115084, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36599230

RESUMO

Due to its low adverse effects, minimal invasiveness, and outstanding patient compliance, photodynamic therapy (PDT) has drawn a great deal of interest, which is achieved through incomplete reduction of O2 by a photosensitizer under light illumination that produces amounts of reactive oxygen species (ROS). However, tumor hypoxia significantly hinders the therapeutic effect of PDT so that tumor cells cannot be eliminated, which results in tumor cells proliferating, invading, and metastasizing. Additionally, O2 consumption during PDT exacerbates hypoxia in tumors, leading to several adverse events after PDT treatment. In recent years, various investigations have focused on conquering or using tumor hypoxia by nanomaterials to amplify PDT efficacy, which is summarized in this review. This comprehensive review's objective is to present novel viewpoints on the advancement of oxygenation nanomaterials in this promising field, which is motivated by hypoxia-associated anti-tumor therapy.


Assuntos
Nanoestruturas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Hipóxia Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia/tratamento farmacológico , Linhagem Celular Tumoral
7.
Hematology ; 27(1): 1003-1009, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36117408

RESUMO

BACKGROUND: Besides the traditional roles of HBA1 and HBB, recent findings suggest that hemoglobin genes may have roles in other contexts. OBJECTIVE: In the present study, we aim to investigate a possible tumor-suppressor role of HBA1 and HBB in acute myeloid leukemia. METHODS: Quantitative real-time PCR (RT-qPCR) was performed to detect the expression levels of HBA1 and HBB in acute myeloid leukemia patients and AML cell lines. The transfected cells were analyzed for Cell Counting Kit-8 (CCK-8), apoptosis, and cell cycle assay. RESULTS: HBA1 and HBB genes were significantly decreased in acute myeloid leukemia patients and AML cell lines. Furthermore, in vitro approaches showed that overexpression of HBA1 and HBB inhibited proliferation, induced cell apoptosis, and blocked cell cycle process at the G2/M phase in K562 cells. CONCLUSION: Our data indicated that HBA1 and HBB genes may be potential tumor-suppressor genes in acute myeloid leukemia.


Assuntos
Hemoglobina A/genética , Hemoglobinas/genética , Leucemia Mieloide Aguda , Proliferação de Células , Hemoglobinas Glicadas , Humanos , Células K562 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo
9.
J Cancer ; 12(7): 1967-1977, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33753995

RESUMO

Objective: Overexpression of vascular endothelial growth factor (VEGF), a major angiogenic factor, was found in myelodysplastic syndromes (MDS) and showed different expression statuses in different risk groups of MDS. We aimed to investigate the possible role of microRNA (miR)-15a and miR-16 on the regulation of VEGF expression and their effect on angiogenesis in lower- and higher-risk MDS. Methods: We studied peripheral blood and bone marrow samples of MDS patients or several leukaemia and MDS cell lines by enzyme-linked immunosorbent assay, immunohistochemical staining, immunofluorescence and quantitative PCR for expression levels of VEGF, miR-15a and miR-16. MiRNA transfection and Luciferase reporter assays were conducted to investigate whether VEGF is a target of miR-16. Migration and tube formation assays were performed in cells exposed to medium from cells with overexpressed or knockdown miR-16. Results: It showed a significantly lower level of miR-16 in higher-risk MDS patients, while the VEGF levels were upregulated. Inverse correlation between VEGF and miR-16 were determined in cells lines including SKM-1, THP-1, and K562 cells. Overexpression of miR-16 in SKM-1 cells resulted in reduced VEGF secretion and cell protein levels. Direct binding of miR-16 to the 3' untranslated region (3'-UTR) of VEGF was confirmed by luciferase reporter assays. The migration and tube formation of human umbilical vein endothelial cells decreased in the presence of medium from SKM-1 cells with overexpressed miR-16. Conclusion: These data suggest that miR-16 may play a role in angiogenesis in higher-risk MDS by targeting VEGF and therefore modulating MDS progression. MiR-16 might be a novel therapeutic target in higher-risk MDS.

10.
Front Med (Lausanne) ; 8: 796920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35145978

RESUMO

BACKGROUND: Aplastic anemia (AA), megaloblastic anemia (MA), and myelodysplastic syndrome (MDS) were common anemic diseases. Sometimes it was difficult to distinguish patients with these diseases. METHODS: In this article, we proposed one measurement method for the area of red blood cells (RBCs) from microscopic images based on image processing technology and analyzed the differences of the area in 25 patients with AA, 64 patients with MA, and 68 patients with MDS. RESULTS: The area of RBCs was 44.19 ± 3.88, 42.09 ± 5.35, 52.87 ± 7.68, and 45.75 ± 8.07 µm2 in normal subjects, patients with AA, MA, and MDS, respectively. The coefficients of variation were 8.78%, 10.05%, 14.53%, and 14.00%, respectively, in these groups. The area of RBCs in patients with MA was significantly higher than normal subjects (p < 0.001). Compared with patients with AA and MDS, the area of RBCs in patients with MA was also significantly higher (p < 0.001). The results of correlation analysis between the area of RBCs and mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), and red cell distribution width showed no significant correlations (p > 0.05). The area under the curve (AUC) results of the Receiver Operating Characteristic (ROC) curves of RBCs area were 0.421, 0.580, and 0.850, respectively, in patients with AA (p = 0.337), MDS (p = 0.237), and MA (p < 0.001). CONCLUSION: Identifying the area of RBCs in peripheral blood smears based on the image processing technology could achieve rapid and efficient diagnostic support for patients with MDS and MA, especially for patients with MA and in combination with MCV. However, a larger sample study is needed to find the cutoff area values.

11.
Haematologica ; 105(10): 2407-2419, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33054081

RESUMO

Adherent neutrophils on vascular endothelium positively contribute to cell-cell aggregation and vaso-occlusion in sickle cell disease. In the present study, we demonstrated that pyridoxamine, a derivative of vitamin B6, might be a therapeutic agent to alleviate intravascular cell-cell aggregation in sickle cell disease. Using real-time intravital microscopy, we found that one oral administration of pyridoxamine dose-dependently increased the rolling influx of neutrophils and reduced neutrophil adhesion to endothelial cells in cremaster microvessels of sickle cell disease mice challenged with hypoxia-reoxygenation. Short-term treatment also mitigated neutrophil-endothelial cell and neutrophil-platelet interactions in the microvessels and improved the survival of sickle cell disease mice challenged with tumor necrosis factor-α. The inhibitory effects of pyridoxamine on intravascular cell-cell interactions were potentiated by co-treatment with hydroxyurea. We observed that long-term (5.5 months) oral treatment with pyridoxamine significantly diminished the adhesive function of neutrophils and platelets and down-regulated the expression of E-selectin and intercellular adhesion molecule-1 on the vascular endothelium in tumor necrosis factor-α-challenged sickle cell disease mice. Ex vivo studies revealed that the surface amount of αMß2 integrin was significantly decreased in stimulated neutrophils isolated from sickle cell disease mice treated with pyridoxamine-containing water. Studies using platelets and neutrophils from sickle cell disease mice and patients suggested that treatment with pyridoxamine reduced the activation state of platelets and neutrophils. These results suggest that pyridoxamine may be a novel therapeutic and a supplement to hydroxyurea to prevent and treat vaco-occlusion events in sickle cell disease.


Assuntos
Anemia Falciforme , Piridoxamina , Anemia Falciforme/tratamento farmacológico , Animais , Adesão Celular , Comunicação Celular , Células Endoteliais , Endotélio Vascular , Humanos , Hidroxiureia , Camundongos , Neutrófilos
12.
Front Oncol ; 10: 1345, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766161

RESUMO

Abnormal coagulation parameters and potential benefits of anticoagulant therapy in general population with novel coronavirus pneumonia (COVID-19) have been reported. However, limited data are available on cancer patients. Coagulation indexes and inflammation parameters in 57 cancer patients with SARS-CoV-2 infection with different severity were retrospectively analyzed. We found that D-dimer levels were increased in 33 patients (57.9%, median: 790 ng/mL). Compared with ordinary type patients, severe and critical ill patients had decreased MPV values (P = 0.006), prolonged PT (median: 13.3 vs. 11.5 vs. 11.4 s, P < 0.001), significant higher D-dimer levels (median: 2,400 vs. 940 vs. 280 ng/mL, P < 0.001), higher PCT levels (median: 0.17 vs. 0.055 vs. 0.045 ng/mL, P = 0.002), higher IL-6 (median: 20.6 vs. 2.3 vs. 3.0 pg/mL, P = 0.040), and decreased PaO2 (median: 68 vs. 84 vs. 96 mm Hg, P < 0.001). Importantly, three patients, one severe and two critical ill type, with increased D-dimer survived after anticoagulant therapy with continuous heparin infusion. Increased D-dimer levels positively correlated with increased PCT levels (r = 0.456, P = 0.002) and IL-6 levels (r = 0.501, P = 0.045). A negative correlation between D-dimer levels and PaO2 levels (r = -0.654, P = 0.021) were also existed. Cancer patients with COVID-19 showed prominent hypercoagulability associated with severe inflammation, anticoagulation therapy might be useful to improve the prognosis and should be immediately used after the onset of hypercoagulability.

13.
Pathology ; 52(5): 552-560, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32571542

RESUMO

Myelodysplastic syndromes (MDS) are characterised by impaired haematopoiesis and a high risk of leukaemic transformation. A decrease in RPS14 expression in non-5q MDS patients was confirmed by immunohistochemical analyses of MDS bone marrow biopsies. To determine the cause of RPS14 reduction in non-5q MDS, we analysed the 3'-UTR of RPS14 and demonstrated that miR-223 binds to the 3'-UTR of RPS14 by bioinformatics-based approach combined with the luciferase reporter assay. Using quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significantly increased expression of miR-223 in CD34+ cells and SKM-1 cells derived from non-5q MDS patients in vitro and demonstrated a correlation between miR-223 levels and red blood cell counts. Exogenous miR-223 expression in SKM-1 cells could also inhibit RPS14 expression. In functional studies, overexpression of miR-223 was shown to promote cell proliferation and inhibit cell apoptosis in SKM-1 cells, and to impair erythroid differentiation in haemin-induced K562 cells. Taken together, our results revealed that the overexpression of miR-223 in MDS is closely associated with cell transformation and erythroid differentiation arrest, which is most likely mediated by targeting RPS14.


Assuntos
Células da Medula Óssea/metabolismo , Proliferação de Células/fisiologia , MicroRNAs/metabolismo , Síndromes Mielodisplásicas/metabolismo , Proteínas Ribossômicas/metabolismo , Apoptose/fisiologia , Células da Medula Óssea/patologia , Linhagem Celular , Sobrevivência Celular/fisiologia , Biologia Computacional , Humanos , MicroRNAs/genética , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas Ribossômicas/genética
14.
Case Reports Hepatol ; 2020: 1659718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32181027

RESUMO

The patient is a 75-year-old man with history of diabetes and hypertension who presented with syncope after experiencing sharp, 10/10 right flank and abdominal pain worsening over three weeks associated with decreased appetite. Physical examination revealed hepatomegaly and right lower quadrant (RUQ) tenderness, negative for peritoneal signs. Bloodwork showed leukocytosis (13 K/mcl), alkaline phosphatase (141 U/L), total bilirubin (2.0 mg/dL), and gamma-glutamyl transferase (172 U/L). Computed Tomography (CT) revealed multiple hepatic cysts with the largest measuring 17 × 14 × 18 cm (Figure 1). Parenteral opiates provided minimal relief. Cardiac and neurologic etiologies of syncope were ruled out. The patient's course was complicated by opioid-induced delirium as his abdominal pain progressively worsened despite escalating doses of parenteral and oral analgesics. Gastroenterology and interventional radiology consulted to evaluate for Glisson's capsular stretch. Therapeutic aspiration yielded 2.5 L of serous fluid, which alleviated the patient's pain. Cytology was negative for malignancy. Opiates were titrated down. Repeat CT (Figure 2) showed cysts that were significantly reduced in size. The patient showed complete resolution of symptoms and was subsequently discharged. We present a rare case of a large hepatic cyst causing syncope. In the appropriate clinical setting, syncope with RUQ tenderness and hepatomegaly should raise the index of suspicion for hepatic cysts.

15.
Clin Lymphoma Myeloma Leuk ; 20(5): 329-339.e3, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32037286

RESUMO

BACKGROUND: Integrating the proportion of ring sideroblasts and SF3B1 mutation status is required for diagnosis of sideroblastic subgroups in myelodysplastic syndrome (MDS) as proposed by the World Health Organization 2016 classification. However, the clinical implications of SF3B1 mutation and ring sideroblasts in MDS-refractory cytopenia with multilineage dysplasia (MDS-RCMD) remain unclear. PATIENTS AND METHODS: Clinical and laboratory features in 238 MDS-RCMD patients were retrospectively analyzed, and the prognostic significance of SF3B1 mutation and ring sideroblasts on overall survival and leukemia-free survival in total MDS-RCMD patients and different subgroups stratified by the percentage of ring sideroblasts or SF3B1 mutation status were evaluated. RESULTS: MDS-RCMD patients with ring sideroblasts ≥ 15% showed a significantly higher prevalence of SF3B1 mutation compared to ring sideroblasts 5%-14% or ring sideroblasts < 5% (75.6% vs. 15.1% vs. 6.4%, P < .001). In multivariate analysis, SF3B1 mutation was associated with a significantly prolonged survival (hazard ratio [HR] = 0.430, P = .013) and reduced leukemic transformation (HR = 0.174, P = .021) in total MDS-RCMD patients, while ring sideroblasts showed no independent effect on either survival or leukemic transformation. There were no significant differences in clinical characteristics or survival between MDS-RCMD patients with ring sideroblasts ≥ 15% and ring sideroblasts 5%-14% in the presence of SF3B1 mutation. Furthermore, SF3B1 mutation showed an independent prognostic effect on overall survival in MDS-RCMD patients with ring sideroblasts 5%-14% (HR = 0.195, P = .046). CONCLUSION: SF3B1 mutation, not the presence of ring sideroblasts, identifies a distinct subtype and showed independent prognostic value on survival and leukemia transformation in MDS-RCMD patients.


Assuntos
Mutação , Síndromes Mielodisplásicas , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Estudos Retrospectivos , Taxa de Sobrevida
16.
Pathology ; 49(5): 526-533, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28669578

RESUMO

In order to evaluate the prognostic value of abnormal localisation of immature precursors (ALIP) and CD34 immunostaining in myelodysplastic syndromes (MDS), bone marrow histopathological features in 187 MDS patients were retrospectively analysed and the prognostic significance of ALIP and CD34 immunostaining on overall survival (OS) and progression to leukaemia-free survival (PFS) in total patients and different Revised-International Prognostic Scoring System (IPSS-R) subgroups were evaluated. In univariate analysis, age ≥60, ALIP, ≥5% CD34+ cells, CD34+ clusters and IPSS-R subgroups were associated with shorter OS (p = 0.027, p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, respectively) and PFS (p = 0.029, p = 0.006, p = 0.001, p < 0.0001, p < 0.0001, respectively). Haemoglobin level had a significant impact on OS (p < 0.0001) but not on PFS (p = 0.054). In multivariate analysis, ALIP, haemoglobin level, ≥5% CD34+ cells, CD34+ clusters and IPSS-R subgroups had independent influence on OS (p = 0.012, p < 0.0001, p = 0.010, p < 0.0001, p < 0.0001, respectively), while only CD34+ clusters and IPSS-R subgroups had independent influence on PFS (p < 0.0001, p = 0.016, respectively). In different IPSS-R subgroups, ALIP could maintain its prognostic impact in lower IPSS-R risk subgroups, while ≥5% CD34+ cells and CD34+ clusters had significant prognostic value in both lower and intermediate-higher IPSS-R risk subgroups. Therefore, CD34+ clusters showed more important prognostic impact on survival and progression to leukaemia.


Assuntos
Antígenos CD34/metabolismo , Síndromes Mielodisplásicas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Medula Óssea/patologia , Criança , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
18.
Biomed Pharmacother ; 69: 76-81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661341

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, though the etiology of the leukemia is poorly understood, both genetic and environmental factors appear to be involved. Previous studies investigating the association between MDR1 C3435T polymorphisms and risk of children with ALL reported controversial results. METHODS: We performed a comprehensive meta-analysis to clarify the effect of MDR1 C3435T polymorphisms on risk of childhood ALL. The strength of the association was measured by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Nine studies were finally included, involving a total of 1462 cases and 1522 controls. There was no association between MDR1 C3435T polymorphism and children ALL risk in all of four models in overall populations (CT vs. CC: OR=0.86, 95% CI=0.65-1.15, P=0.310; TT vs. CC: OR=1.50, 95% CI=0.96-2.35, P=0.076; TT/CT vs. CC: OR=1.12, 95% CI=0.95-1.33, P=0.166; TT vs. CC/CT: OR=1.58, 95% CI=0.97-2.56, P=0.067). Subgroup analysis by race suggested that this association existed in Asians under the under the homozygote model and recessive model (TT vs. CC: OR=2.45, 95% CI=1.24-4.86, P=0.010; TT vs. CT/CC: OR=2.65, 95% CI=1.22-5.75, P=0.014). CONCLUSIONS: This meta-analysis suggests there was no association between MDR1 C3435T polymorphism and children ALL risk in overall populations, but significant association with an increased risk in Asians.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Criança , Etnicidade/genética , Heterogeneidade Genética , Humanos , Modelos Genéticos , Razão de Chances , Viés de Publicação , Fatores de Risco
19.
Acta Histochem ; 116(6): 1113-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24958342

RESUMO

In view of the importance of Auer rods in the rapid diagnosis of acute promyelocytic leukemia, we compared the results of Wright-Giemsa stain and Liu's stain (a rapid and simple stain, which is also a kind of modified Romanowsky stain) in the detection of Auer rods. This study was based on 53 cases of acute promyelocytic leukemia. Two staining methods were respectively performed on the bone marrow smears of these cases, and presence of Auer rods as well as nuclear features, cytoplasmic features and the degree of granularity of the cytoplasm were compared in each case. Our results showed that the occurrence of Auer rods as well as faggots in leukemic promyelocytes were significantly higher under Liu's stain than under Wright-Giemsa stain. Significant differences also existed in the occurrence of hypergranular cells and cytoplasmic protrusions between smears stained with Liu's stain and Wright-Giemsa stain. Liu's stain is important for the rapid diagnosis of suspicious APL, especially in recognizing Auer rods.


Assuntos
Corantes Azur/química , Grânulos Citoplasmáticos/patologia , Amarelo de Eosina-(YS)/química , Leucemia Promielocítica Aguda/patologia , Coloração e Rotulagem/métodos , Antígenos CD/metabolismo , Humanos
20.
Acta Haematol ; 131(2): 126-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24158033

RESUMO

OBJECTIVE: It was our aim to study the diagnostic significances of various dysplasia characteristics in myelodysplastic syndrome (MDS). METHODS: We analyzed 160 cases of primary MDS and a control group including 28 cases of paroxysmal nocturnal hemoglobinuria (PNH), 104 cases of idiopathic thrombocytopenic purpura (ITP), 53 cases of non-severe aplastic anemia (NSAA), 40 cases of megaloblastic anemia and 50 cases of infectious and autoimmune diseases. Peripheral blood smears and bone marrow morphology were reviewed. RESULTS: There was no significant difference in the occurrence rates of a variety of dysplasias in three lineages among MDS, megaloblastic anemia and PNH; however, changes in qualities and quantities in three lineages between NSAA and MDS were significantly different. ITP and MDS showed statistical differences in multiple changes in myeloid and erythroid cells. Significant differences also existed in multiple changes in erythroid series and megakaryocytes between infectious and autoimmune diseases and MDS. Morphological abnormalities highly related with MDS included multinucleated erythroblasts, ringed sideroblasts, poikilocytosis and gigantocytes, pseudo-Pelger neutrophils, ring-shaped nucleus, and micromegakaryocytes. CONCLUSIONS: It is difficult to discriminate megaloblastic anemia and PNH from MDS by means of cell morphology. Different dysplasias of MDS have specific diagnostic values.


Assuntos
Povo Asiático , Medula Óssea/patologia , Síndromes Mielodisplásicas/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Megaloblástica/sangue , Anemia Megaloblástica/etnologia , Anemia Megaloblástica/patologia , Doenças Autoimunes/sangue , Doenças Autoimunes/etnologia , Doenças Autoimunes/patologia , Contagem de Células , Linhagem da Célula , Tamanho Celular , China , Células Eritroides/patologia , Feminino , Células Gigantes/patologia , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/etnologia , Hemoglobinúria Paroxística/patologia , Humanos , Infecções/sangue , Infecções/etnologia , Infecções/patologia , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Células Mieloides/patologia , Neutrófilos/patologia , Reação do Azul da Prússia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/etnologia , Púrpura Trombocitopênica Idiopática/patologia , Coloração e Rotulagem , Adulto Jovem
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