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BACKGROUND: Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50â×â109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. FINDINGS: Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. INTERPRETATION: Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. FUNDING: HUTCHMED and Science and Technology Commission of Shanghai Municipality.
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Púrpura Trombocitopénica Idiopática , Humanos , Persona de Mediana Edad , Masculino , Femenino , Método Doble Ciego , Adulto , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , China , Anciano , Resultado del Tratamiento , Enfermedad Crónica , Adulto Joven , Adolescente , Recuento de Plaquetas , Quinasa Syk/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Background: Acute myeloid leukemia (AML) is a challenging disease with high rates of recurrence. The role of the cancer-related gene GRHL2 in AML has not been widely studied. Methods: Peripheral blood samples were collected from 73 AML patients and 68 healthy controls. Droplet digital PCR was used to detect GRHL2 methylation levels to explore the value of GRHL2 methylation in the diagnosis, treatment response and prognosis of AML. Result: GRHL2 methylation was significantly increased in AML patients (p < 0.01), with high diagnostic accuracy (area under the curve: 0.848; p < 0.001). GRHL2 methylation was correlated with chemotherapy response (p < 0.05) and is an independent prognostic factor for AML (p < 0.05). Conclusion: GRHL2 methylation is expected to serve as a biomarker for diagnosing AML patients and predicting prognosis.
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Metilación de ADN , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Pronóstico , Biomarcadores , Reacción en Cadena de la Polimerasa , Proteínas de Unión al ADN/genética , Factores de Transcripción/genéticaAsunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Sistema de Registros , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Anemia Aplásica/terapia , Anemia Aplásica/mortalidad , Anemia Aplásica/diagnóstico , Anciano , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , China/epidemiología , Pueblos del Este de AsiaRESUMEN
This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.
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Mieloma Múltiple , Talidomida/análogos & derivados , Humanos , Adulto , Persona de Mediana Edad , Anciano , Mieloma Múltiple/tratamiento farmacológico , Dexametasona , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Background: We investigated the effect of human serum albumin (HSA) on human umbilical cord blood (UCB) CD34+ hematopoietic stem/progenitor cells (HSPCs) cultured in vitro and transplanted in vivo. Methods: Human umbilical cord blood mononuclear cells were obtained by density gradient centrifugation. CD34+ cells were then sorted by CD34 conjugated magnetic microbeads. The sorted cells were cultured with or without HSA for 8 days in vitro. After 8 days, all cells were harvested for flow phenotyping and colony formation cell (CFC) experiments. The cells were injected into immunodeficient mice (NOD/Shi-scid/IL2Rγnull, NOG) via intravenous injections. From 4 weeks post-transplantation, flow cytometry was used to calculate human cell chimerism in the peripheral blood (PB) every 2 weeks. Flow phenotyping of human cell chimerism in bone marrow and spleen was calculated 16 weeks post-transplantation. Results: Compared to the control group, CD34+ cells cultured with HSA increased significantly in vitro. The long-term engraftment of HSPCs and the hematopoietic multilineage reconstruction capacity were preserved by HSA. Normal engraftment of human cells could be maintained via HSA treatment could maintain normal engraftment of human cells in recipient PB. Conclusions: Here, we found that HSA was beneficial to maintaining CD34+ cell expansion and short-term colony formation in vitro and optimizing multilineage reconstitution in immunodeficient mice in vivo.
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Purpose: Abnormal methylation of Grainyhead-like 2 (GRHL2) is associated with a substantial role in the malignant phenotype of tumor patients. Our present research is aimed at studying the abnormal expression of GRHL2 and the association of methylation in patients with acute leukemia and its relationship with prognosis. Materials and Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) for detecting the aberrant expression level of GRHL2 in 60 patients with acute leukemia and 60 normal controls. We analyzed the significant correlation between the expression level of GRHL2 with clinicopathological features and patients' prognosis in acute leukemia using the corresponding statistical methods. Secondly, we employed qRT-PCR and Western blotting to detect the mRNA and protein levels of GRHL2 in leukemia cell lines. Next, we used methylation-specific polymerase chain reaction (MSP) technology for detecting the methylation of GRHL2 in clinical samples with acute leukemia and cell lines. Then we investigated the demethylating effect of arsenic trioxide and 5-azacitidine on the mRNA and protein expression levels of GRHL2 in cell lines of acute leukemia. Finally, we studied the effects of arsenide trioxide and 5-azacitidine on the proliferation of leukemia cells and the TGF-ß signaling pathway. Results: We found a lower level of GRHL2 expression not only in acute leukemia patients but also in cell lines when compared with normal controls. At the same time, the expression level of GRHL2 in patients with acute leukemia was significantly correlated with leukocyte count, platelet count, and cytogenetic risk grouping. In addition, the lower GRHL2 expression group showed a significantly lower overall survival rate in acute leukemia patients than that of patients with a higher GRHL2 expression group. Univariate and multivariate analyses revealed that the expression of GRHL2 is an independent risk factor in acute leukemia patients. The methylation level of the GRHL2 promoter region in acute leukemia patients and cell lines was significantly higher than the normal control group, and we found the elevated mRNA and protein levels of GRHL2 in acute leukemia cell lines after the use of the demethylation drug arsenic trioxide and 5-azacitidine. At the same time, arsenide trioxide and 5-azacitidine are associated with the inhibition of cellular proliferation of acute leukemia cells and also promote the elevated expression of TGF-ß signaling pathway-linked proteins, including TGF-ß, Smad2, Smad3, and Smad4. Conclusion: Increased expression and methylation level of GRHL2 are closely associated with the prognosis and malignant phenotype of acute leukemia patients and play an irreplaceable role in the occurrence and development of patients with acute leukemia.
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Acute Myeloid Leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. Recent studies indicated that endocrine disruptor chemicals (EDCs) are potential risk factors for AML progression. Our present data showed that an industrial endocrine disrupting chemical, Benzyl butyl phthalate (BBP), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin (DNR) and cytarabine (Ara-C) treatments. Further, BBP can increase the glucose consumption, lactate generation, and ATP levels of AML cells. Among the measured glycolysis-related genes, BBP can increase the expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), a mitochondrial protein that regulates the tricarboxylic acid cycle (TCA) cycle. The inhibitor of PDK4 or its specific siRNA can attenuate BBP-induced cell proliferation and ATP generation, which suggested the essential roles of PDK4 in BBP-induced glycolysis and proliferation. Further, BBP can increase the mRNA stability of PDK4, while had no effect on its transcription and protein stability. miR-15b-5p can bind with the 3'UTR of PDK4 to decrease its mRNA stability, while BBP can decrease the expression of miR-15b-5p in AML cells. Collectively, our data showed that BBP can trigger the malignancy of AML cells via regulation of miR-15b-5p/PDK4 signals.
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Carcinógenos/toxicidad , Leucemia Mieloide Aguda/inducido químicamente , Ácidos Ftálicos/toxicidad , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/biosíntesis , Regiones no Traducidas 5'/genética , Adenosina Trifosfato/biosíntesis , Antibióticos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citarabina/farmacología , Daunorrubicina/farmacología , Regulación Neoplásica de la Expresión Génica , Glucólisis/efectos de los fármacos , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , MicroARNs/genética , MicroARNs/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/efectos de los fármacos , ARN Interferente Pequeño/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Diffuse large B cell lymphoma (DLBCL), an aggressive cancer of the B cells, is the most common subtype of non-Hodgkin lymphoma (NHL) worldwide. In China, the cases of DLBCL increase yearly. C-X-C chemokine receptor 4 (CXCR4) has been implicated in the migration and trafficking of malignant B cells in several hematological malignancies, and only a few reports have been published on the role of CXCR4 in the metastasis of DLBCL. This review summarizes the relevant perspectives on the functional mechanism, prognostic significance, and therapeutic applications of the CXCL12/CXCR4 axis in DLBCL, in particular DLBCL with bone marrow involvement.
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Médula Ósea/metabolismo , Movimiento Celular , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/terapia , Proteínas de Neoplasias/metabolismo , Receptores CXCR4/metabolismo , Médula Ósea/patología , Quimiocina CXCL12/metabolismo , China/epidemiología , Humanos , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/patología , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment. MATERIALS AND METHODS: In this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined. RESULTS: There was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60. CONCLUSIONS: The expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia.
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Immature colon carcinoma transcript 1 (ICT1), a human mitochondrial translation release factor, is a ribosome-dependent codon-independent peptidyl-tRNA hydrolase. ICT1-deficiency has been recognized as a cell growth inhibitor of hepatoblastoma and glioblastoma multiforme. To explore the role of ICT1 in human leukemia, 2 short hairpin RNAs (shRNAs) targeting ICT1 sequences were designed in leukemia U937 cells. The successful infection of ICT1 in the U937 cells was observed under a fluorescence microscope and further quantified by western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tetrazolium dye (MTT) assay revealed a significant decrease in proliferation of ICT1-knockdown U937 cells on the fourth and fifth day as compared with the control. Depletion of ICT1 resulted in an increase in S phase and sub-G1 (representing cell apoptosis) fractions. Annexin V-APC/7-AAD staining assay confirmed that knockdown of ICT1 played a crucial role in boosting early and late apoptotic programs in U937 cells. Downregulation of ICT1 also altered cyclin A2 transcription expression, caspase-3 activity and p21 protein expression. Additionally, decreased levels of heat shock protein 27 (HSP27) phosphorylation at Ser78 was correlated with knockdown of ICT1 in U937 cells. Thus, we concluded that the regulatory role of ICT1 in leukemia may be used as a potential therapeutic target for the treatment of leukemia.
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Biomarcadores de Tumor/metabolismo , Puntos de Control del Ciclo Celular , Proliferación Celular , Leucemia/patología , Proteínas/antagonistas & inhibidores , Fase S , Apoptosis , Biomarcadores de Tumor/genética , Humanos , Leucemia/genética , Leucemia/metabolismo , Proteínas/genética , Proteínas Ribosómicas , Células Tumorales CultivadasRESUMEN
Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.
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Proliferación Celular , Factor 3 de Iniciación Eucariótica/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/metabolismo , Factor 3 de Iniciación Eucariótica/genética , Técnicas de Silenciamiento del Gen , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteínas de Neoplasias/genética , Células U937RESUMEN
BACKGROUND: Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia. METHODS: Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot. RESULTS: The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p<0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p<0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p<0.01). CONCLUSION: When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS.
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Albúminas/uso terapéutico , Organismos Acuáticos/química , Medicamentos Herbarios Chinos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Calidad de Vida , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adulto , Albúminas/farmacología , Proteínas de Unión al Calcio/metabolismo , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Células K562 , Leucemia Mieloide Aguda/genética , Placebos , RecurrenciaRESUMEN
Ribosomal protein S15a (RPS15A), which is a component of the 40S ribosomal subunit, is able to promote mRNA/ribosome interaction during the early stage of translation. Previous studies have demonstrated that RPS15A regulates cell growth and is involved in several types of human cancer. The aim of the present study was to investigate the role of RPS15A in acute myeloid leukemia (AML). Lentivirusdelivered short hairpin RNA (shRNA) was used to silence RPS15A expression in the U937 AML cell line. Subsequently, the effects of RPS15A silencing on cell viability, cell cycle progression and apoptosis were investigated. The results indicated that RPS15A knockdown significantly inhibited cell growth. Furthermore, flow cytometric analysis demonstrated that the majority of U937 cells were arrested in G0/G1 phase and subG1 phase after RPS15A knockdown, as determined using propidium iodide staining. In addition, U937 cells underwent apoptosis in response to RPS15A silencing, as determined using Annexin V/7aminoactinomycin D staining. In conclusion, the present study provides novel evidence indicating that RPS15A modulates AML cell growth in vitro, and may be considered a novel therapeutic target for the treatment of AML.
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Apoptosis , Puntos de Control de la Fase G1 del Ciclo Celular , Silenciador del Gen , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , ARN Interferente Pequeño/biosíntesis , Fase de Descanso del Ciclo Celular , Proteínas Ribosómicas/antagonistas & inhibidores , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Interferente Pequeño/genética , Proteínas Ribosómicas/biosíntesis , Proteínas Ribosómicas/genética , Células U937RESUMEN
OBJECTIVE: To investigate the expression of PD-1 and TIM-3 in CD3+ T cells in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on data from 46 patients with newly diagnosed DLBCL and 30 healthy people. Flow cytometry was used to detect the expression of PD-1 and TIM-3 before and after chemotherapy. RESULTS: Compared to healthy control, the expression of PD-1 and TIM-3 in patients with DLBCL was increased in CD3+ T cells. There is no significant change of PD-1 and TIM-3 in patients with stage I/II DLBCL, however, they were markedly increased in patients with stage III/IV DLBCL. The expression of PD-1 and TIM-3 elevated in DLBCL patients with B symptoms, IPI score >2 points and high level of LDH and Ki-67. After four courses of standard chemotherapy, PD-1 and TIM-3 expression level decreased. The treatment efficiency is higher in patients with low expression of PD-1 and TIM-3 than in patients with high PD-1 and TIM-3 expression. CONCLUSION: DLBCL patients have high expression level of PD-1 and TIM-3, which are related to DLBCL staging. PD-1 and TIM-3 expression levels are also related to the efficiency of chemotherapy. PD-1 and TIM-3 expression levels may be used as an indicator of chemotherapeutic efficacy in patients with DLBCL.
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Biomarcadores de Tumor/metabolismo , Complejo CD3/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Proteínas de la Membrana/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/metabolismo , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Citometría de Flujo , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Masculino , Estadificación de Neoplasias , Prednisona/uso terapéutico , Estudios Retrospectivos , Rituximab , Linfocitos T/inmunología , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
Bone marrow stromal cells (BMSCs) may differentiate into nerve cells under a certain condition; however, the clinical application for treating nervous system disease remains unclear. The aim is to assess the safety profile, feasibility, and effectiveness of surgery combined with autologous BMSCs transplantation for treating ICH. 206 ICH patients who had received surgical procedure were divided into transplantation (n = 110) or control group (n = 96). For transplantation group, BMSCs were injected into the perihemorrhage area in the base ganglia through an intracranial drainage tube 5.5 (3.01-6.89) days after surgery, followed by a second injection into the subarachnoid space through lumbar puncture 4 weeks later. Neurologic impairment and daily activities were assessed with National Institute Stroke Scale (NIHSS), Barthel index, and Rankin scale before transplantation and 6 months and 12 months after transplantation. Our results revealed that, compared with control group, NIHSS score and Rankin scale were both significantly decreased but Barthel index was increased in transplantation group after 6 months. Interestingly, no significant difference was observed between 12 months and 6 months. No transplantation-related adverse effects were investigated during follow-up assessments. Our findings suggest that surgery combined with autologous BMSCs transplantation is safe for treatment of ICH, providing short-term therapeutic benefits.
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T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) plays a critical role in immune tolerance by suppressing the activation and proliferation of T cells. The purpose of this study was to investigate the effect of Tim-3 on the development of diffuse large B cell lymphoma (DLBCL). A total of 40 newly diagnosed DLBCL patients and 30 healthy donors were recruited. Tim-3 expression on peripheral CD4+ T and CD8+ T cells was analyzed by flow cytometry. Data showed that expression of Tim-3 was significantly increased on both CD4+ and CD8+ T cells in DLBCL patients than in healthy controls (P < 0.001 and P < 0.001, respectively). Also, level of Tim-3 on CD4+ T cells was positively correlated with CD8+ T cells in patients (P < 0.001). Further analyses revealed that patients with advanced tumor stages had elevated Tim-3 expression on CD4+ and CD8+ T cells compared to those with primary tumor stages. In addition, levels of Tim-3 on CD4+ and CD8+ T cells were significantly elevated in DLBCL patients with bone marrow involvement or B symptoms. Our results suggest that Tim-3 is involved in the development of DLBCL.
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Linfoma de Células B Grandes Difuso/inmunología , Proteínas de la Membrana/fisiología , Linfocitos T/metabolismo , Adulto , Anciano , Femenino , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Linfoma de Células B Grandes Difuso/etiología , Linfoma de Células B Grandes Difuso/patología , Masculino , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
Fibroblast growth factor receptor 4 (FGFR4) is expressed in various cell types and plays important roles in regulating immune responses. Evidence has shown that FGFR4 rs351855 (Gly388Arg) polymorphism may act as a risk factor for many diseases. In the current study, we investigated the association between FGFR4 polymorphisms and the susceptibility to non-Hodgkin's lymphoma (NHL) in the Chinese population. Two polymorphisms in the FGFR4 gene (rs351855G/A and rs147603016G/A) were detected by polymerase chain reaction-restriction fragment length polymorphism in 421 NHL cases and 486 healthy controls. Results showed that prevalence of rs351855AA genotype was significantly increased in patients than in controls (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.91-3.23, P < 0.001). Similarly, rs351855A allele presented significantly higher numbers in cases compared to healthy donors (49.8 versus 40.1%, P < 0.001). Further study revealed that the frequency of the rs351855G/A polymorphism was clearly elevated in cases with B cell subtype than those with T cell subtypes. When analyzing the survival time of NHL patients with FGFR4 rs351855G/A polymorphism, cases with AA genotype had significantly shorter survival time compared to the patients with GG genotype (P < 0.001) or GA genotype (P < 0.001). These results suggest that FGFR4 rs351855G/A polymorphism is associated with increased susceptibility to NHL and could be used as a marker for predicting the prognosis of the malignancy.
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Predisposición Genética a la Enfermedad , Linfoma no Hodgkin/genética , Polimorfismo de Nucleótido Simple , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Adulto , Anciano , Femenino , Genotipo , Humanos , Linfoma no Hodgkin/etiología , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , RiesgoRESUMEN
OBJECTIVES: To investigate the effect of a seashell protein Haishengsu (HSS), an extract from a shellfish Tegillarca granosa, on cell growth and the expression of apoptosis genes in leukemia K562 cells. METHODS: Cultured K562 cells were treated with HSS at various concentrations (10-40 mg/L). The cell cycle, cell growth and the expression of apoptosis suppressor gene bcl-2 and apoptosis promoting gene bax were evaluated. RESULTS: HSS, 20mg/L, inhibited cell cycle in the G0/G1 and S phases. HSS, 20mg/L, also inhibited the growth of K562 cells over time. Expression of bcl-2 gene in the HSS 20mg/L (58.8%+/-4.7%) and HSS 40 mg/L group (26.6%+/-2.1%) were lower than in the control group (91.0+/-8.7%, P < 0.01). Expression of bax gene in the HSS 20mg/L (77.7+/-3.6%) and 40 mg/L group (90.6+/-3.7%) were higher than in the control group (10.9+/-6.6%, P < 0.01). CONCLUSION: HSS suppresses leukemia K562 cell growth by inhibiting the G0/G1 and S phases of the cell cycle. It also induces apoptosis in these leukemia cells by reducing the expression of apoptosis suppressor gene bcl-2, and increasing the expression of apoptosis promoting gene bax. Further studies are required to investigate the clinical efficacy of HSS in leukemia.