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Substantial numbers of somatic mutations have been found to accumulate with age in different human tissues. Clonal cellular amplification of some of these mutations can cause cancer and other diseases. However, it is as yet unclear if and to what extent an increased burden of random mutations can affect cellular function without clonal amplification. We tested this in cell culture, which avoids the limitation that an increased mutation burden in vivo typically leads to cancer. We performed single-cell whole-genome sequencing of primary fibroblasts from DNA mismatch repair (MMR) deficient Msh2-/- mice and littermate control animals after long-term passaging. Apart from analyzing somatic mutation burden we analyzed clonality, mutational signatures, and hotspots in the genome, characterizing the complete landscape of somatic mutagenesis in normal and MMR-deficient mouse primary fibroblasts during passaging. While growth rate of Msh2-/- fibroblasts was not significantly different from the controls, the number of de novo single-nucleotide variants (SNVs) increased linearly up until at least 30,000 SNVs per cell, with the frequency of small insertions and deletions (INDELs) plateauing in the Msh2-/- fibroblasts to about 10,000 INDELS per cell. We provide evidence for negative selection and large-scale mutation-driven population changes, including significant clonal expansion of preexisting mutations and widespread cell-strain-specific hotspots. Overall, our results provide evidence that increased somatic mutation burden drives significant cell evolutionary changes in a dynamic cell culture system without significant effects on growth. Since similar selection processes against mutations preventing organ and tissue dysfunction during aging are difficult to envision, these results suggest that increased somatic mutation burden can play a causal role in aging and diseases other than cancer.
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BACKGROUND: Different pulp capping materials have different origins and compositions, require different preparations, and may vary in their bioactive properties. AIM: The purpose of this study was to evaluate the antibacterial activity, biocompatibility, and mineralization-inducing potential of calcium silicate-based pulp capping materials. DESIGN: Six contemporary calcium silicate-based cements, ProRoot MTA, MTA Angelus, Biodentine, EndoSequence, NeoMTA 2, and NeoPutty, were evaluated. The antibacterial effects of these materials against Streptococcus mutans UA159 and Enterococcus faecalis ATCC 29212 were determined by the agar diffusion assay and the direct culture test. The biocompatibility and mineralization-inducing potential of these materials in preodontoblastic 17IIA11 cells were evaluated by the MTT assay and by Alizarin Red S staining, respectively. RESULTS AND CONCLUSION: In agar diffusion test, only Biodentine showed distinct antibacterial effects against S. mutans. All the tested materials, however, showed antibacterial effects against S. mutans and E. faecalis in the direct culture test, with Biodentine showing the strongest growth inhibition against both S. mutans and E. faecalis. All the tested materials showed acceptable biocompatibility and mineralization-supporting potential in our experimental conditions. In summary, ProRoot MTA, MTA Angelus, Biodentine, EndoSequence, NeoMTA 2, and NeoPutty demonstrated acceptable in vitro antimicrobial, biocompatible, and mineralization-supporting properties.
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The six subunit Origin Recognition Complex (ORC) is essential for loading MCM2-7 at origins of DNA replication to promote initiation of DNA replication in organisms ranging from S. cerevisiae to humans. In rare instances, as in cancer cell-lines in culture with mutations in ORC1 , ORC2 or ORC5 , or in endo-reduplicating mouse hepatocytes in vivo without ORC1 , DNA replication has been observed in the virtual absence of individual ORC subunits. Although ORC1 is dispensable in the mouse liver for endo-reduplication, because of the homology of ORC1 with CDC6, it could be argued that CDC6 was substituting for ORC1 to restore functional ORC. Here, we have created mice with a conditional deletion of ORC2 , to demonstrate that mouse embryo fibroblasts require ORC2 for proliferation, but that the mouse hepatocytes can carry out DNA synthesis in vitro and endo-reduplicate in vivo , despite the deletion of ORC2 . Combining the conditional mutation of ORC1 and ORC2 revealed that the mouse liver can still carry out endo-reduplication despite the deletion of the two genes, both during normal development and after partial hepatectomy. Since endo-reduplication, like normal S phase replication, requires the presence of MCM2-7 on the chromatin, these results suggest that in primary hepatocytes there is a mechanism to load sufficient MCM2-7 to carry out effective DNA replication despite the virtual absence of two subunits of ORC.
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Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.
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Acetilcisteína , Acrilamida , Adulto , Niño , Humanos , Acrilamida/toxicidad , Biomarcadores/orina , Encuestas y CuestionariosRESUMEN
Introduction: The aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer's disease (AD) through gene expression changes. Methods: The GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aß1-42 on the expression profile of representative genes in vitro. Results: Based on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aß1-42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aß1-42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased. Discussion: The establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer's disease.
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The capture of colloidal fine suspended particles by vegetation plays an important role in water quality of the shallow aquatic system under rainfall. Quantifying impact of rainfall intensity and vegetation condition on this process remains poorly characterized. In this study, the colloidal particle capture rates under three rainfall intensities, four vegetation densities and with submerged or emergent vegetation were investigated in different travel distance in a laboratory flume. Considering vegetation as porous media, non-Darcy's law with rainfall as a source term, was coupled with colloid first-order deposition model, to simulate the particle concentration changes with time, determining the particle deposition rate coefficient (kd), representing capture rate. We found that the kd increased linearly with rainfall intensity; but increased and then decreased with vegetation density, suggesting the existence of optimum vegetation density. The kd of submerged vegetation is slightly higher than emergent vegetation. The single collector efficiency (η) showed the same trend as kd, suggesting colloid filtration theory well explained the impact of rainfall intensity and vegetation condition. Flow hydrodynamic enhanced the kd trend, e.g., the theoretical strongest flow eddy structure represented in the optimum vegetation density. This study is helpful for the design of wetland under rainfall, to remove colloidal suspended particles and the hazardous material, for the protection of the downstream water quality.
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Coloides , PorosidadRESUMEN
Contaminants can co-exist and migrate together in the environment, causing complex (and sometimes unexpected) transport dynamics which challenge the efficient remediation of individual contaminants. The co-transport dynamics, however, remained obscure for some contaminants, such as arsenic and micro/nano-plastics (MNPs). To fill this knowledge gap, this study explored the co-transport dynamics of arsenic and MNP particles in saturated soil by combining laboratory experiments and stochastic model analysis. Isothermal adsorption and sand column transport experiments showed that the adsorption of arsenic by MNP particles followed the Freundlich model, with a maximum adsorption of 2.425 mg/g for the MNP particles with a diameter of 100 nm. In the presence of MNP particles, the efflux concentration of arsenic ions declined due to adsorption, where the decline rate decreased with the increasing MNP size and increased with the increasing adsorption capacity. Experimental results also showed that the 100 nm nano-plastic particles prohibited arsenic transport in saturated sand columns, while the 5 µm microplastics enhanced arsenic transport due to electrostatic adsorption and media pore plugging. A tempered time fractional advective-dispersion equation was then proposed to quantify the observed breakthrough curves of arsenic. The results showed that this model can reliably capture the co-transport behavior of arsenic with MNPs in the saturated soil with all coefficients of determination over 0.97, and particularly, the small MNP particles facilitated anomalous transport of arsenic. This study therefore improved the understanding and quantification of the co-transport of arsenic and MNPs in soil.
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Arsénico , Suelo , Arsénico/análisis , Arena , Microplásticos , Plásticos , AdsorciónRESUMEN
Cover cropping is commonly acknowledged to promote soil health in agriculture. However, contradictory findings on the benefits of cover crops for soil health, crop productivity, economic and ecological factors, as well as the influence of inherent soil parameters on such benefits exist in the scientific literature. Here, we critically assessed evidence of cover crop benefits through a systematic review of the published literature. To access relevant papers, we searched the literature for cover crops and soil health indicators using Scopus (1996-2020), ScienceDirect (1996-2020) and Google scholar (1970-1996) with specific keywords and combinations. Only English research papers including experimental plots and control groups were considered. We analyzed 102 unique peer-reviewed papers and 1494 corresponding unique plots encompassing various cover crops, soil textures, climates, management systems and experimental duration (1-3 years, 4-6 years, 7-10 years and over 10 years). Strong evidence suggests that cover crops can enhance soil structure and promote soil health by improving soil physical and chemical properties, including saturated hydraulic conductivity (mean net change of 105.6 %), total organic carbon (10.1 %), and total nitrogen (20.2 %). On the other hand, cover crops exhibit weak effects on properties like bulk density and microporosity with fairly low values of net change. In most cases, cover crops increase the soil carbon content, including microbial biomass carbon (19.5 %) and particulate organic carbon (49.5 %). In this systematic review, we found limited studies on the effect of cover crops on soil health as influenced by soil texture, regional climate, rainfall and duration of the cover crop practices. The paucity of long-term regional systematic research of soil physics, chemistry and biology makes it difficult to forecast future implications of cover crops on soil health indicators.
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Agricultura , Suelo , Suelo/química , Producción de Cultivos , Productos Agrícolas , CarbonoRESUMEN
Osteoclasts are the principal bone resorption cells crucial for homeostatic bone remodeling and pathological bone destruction. Increasing data demonstrate a vital role of histone methylation in osteoclastogenesis. As an integral core subunit of H3K4 methyltransferases, Dpy30 is notal as a key chromatin regulator for cell growth and differentiation and stem cell fate determination, particularly in the hematopoietic system. However, its role in osteoclastogenesis is currently unknown. Herein, we generated Dpy30F/F; LysM-Cre+/+ mice, which deletes Dpy30 in myeloid cells, to characterize its involvement in osteoclast differentiation and function. Dpy30F/F; LysM-Cre+/+ mice showed increased bone mass, evident by impaired osteoclastogenesis and defective osteoclast activity, but no alteration of osteoblast numbers and bone formation. Additionally, our ex vivo analysis showed that the loss of Dpy30 significantly impedes osteoclast differentiation and suppresses osteoclast-related gene expression. Moreover, Dpy30 deficiency significantly decreased the enrichment of H3K4me3 on the promoter region of NFATc1. Thus, we revealed a novel role for Dpy30 in osteoclastogenesis through epigenetic mechanisms, and that it could potentially be a therapeutic target for bone destruction diseases.
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Resorción Ósea , Osteólisis , Animales , Resorción Ósea/patología , Diferenciación Celular/genética , Cromatina/metabolismo , Hematopoyesis/genética , Ratones , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Osteogénesis/genética , Osteólisis/metabolismo , Ligando RANK/metabolismoRESUMEN
Periodontitis is a dysbiotic infectious disease that leads to the destruction of tooth supporting tissues. There is increasing evidence that periodontitis may affect the development and severity of Alzheimer's disease (AD). However, the mechanism(s) by which periodontal infection impacts the neurodegenerative process in AD remains unclear. In the present study, using an amyloid precursor protein (APP) knock-in (App KI) AD mouse model, we showed that oral infection with Porphyromonas gingivalis (Pg), a keystone pathogen of periodontitis, worsened behavioral and cognitive impairment and accelerated amyloid beta (Aß) accumulation in AD mice, thus unquestionably and significantly aggravating AD. We also provide new evidence that the neuroinflammatory status established by AD, is greatly complicated by periodontal infection and the consequential entry of Pg into the brain via Aß-primed microglial activation, and that Pg-induced brain overactivation of complement C1q is critical for periodontitis-associated acceleration of AD progression by amplifying microglial activation, neuroinflammation, and tagging synapses for microglial engulfment. Our study renders support for the importance of periodontal infection in the innate immune regulation of AD and the possibility of targeting microbial etiology and periodontal treatment to ameliorate the clinical manifestation of AD and lower AD prevalence.
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Enfermedad de Alzheimer/metabolismo , Complemento C1q/metabolismo , Microglía/metabolismo , Periodontitis/metabolismo , Periodontitis/microbiología , Sinapsis/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Porphyromonas gingivalisRESUMEN
OBJECTIVE: To establish a workflow for isolating single trophectoderm (TE) and inner cell mass (ICM) cells and to simultaneously evaluate these cells for copy number variation (CNV) as well as methylome development. DESIGN: Experimental. SETTING: Academic medical center. PATIENT(S): Donated genetically abnormal blastocysts. INTERVENTION(S): Single cells were isolated, followed by bisulfite conversion and sequencing to identify CNV and methylome profiles. MAIN OUTCOME MEASURE(S): CNV and methylation profiling. RESULT(S): Two embryos were dissociated, isolating 46 single cells, with 17 ICM and 12 TE cells selected for further downstream analysis. Chromosome ploidies and embryo sex were concordant with the results from conventional aneuploidy testing. In 3 of the 29 cells, additional aneuploidies were discovered, indicating possible mosaicism undetected by routine preimplantation genetic testing for aneuploidy. CpG methylation frequency was higher in ICM cells compared with TE cells (44.3% vs. 32.4%), respectively, while non-CpG methylation frequency was similar among both cell types. CpG methylation levels accurately distinguished ICM from TE cells epigenetically. CONCLUSION(S): We describe an effective workflow for isolating and sequencing single ICM and TE cells from human blastocysts. The use of methylation profiling can help distinguish these two cell populations better then morphologic identification alone. TE cells had significantly lower levels of DNA methylation, which may be explained in part by the fact that these cells have begun the process of differentiation and are transcriptionally more active than ICM. This approach may be used to explore the genetic complexities within human embryos, specifically among the two primary cell types seen at this stage of development.
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Masa Celular Interna del Blastocisto/patología , Variaciones en el Número de Copia de ADN , Metilación de ADN , Epigénesis Genética , Epigenoma , Epigenómica , Dosificación de Gen , Análisis de la Célula Individual , Trofoblastos/patología , Aneuploidia , Masa Celular Interna del Blastocisto/metabolismo , Separación Celular , Islas de CpG , Femenino , Regulación del Desarrollo de la Expresión Génica , Humanos , Trofoblastos/metabolismo , Secuenciación Completa del Genoma , Flujo de TrabajoRESUMEN
Identification of de novo copy number variations (CNVs) across the genome in single cells requires single-cell whole-genome amplification (WGA) and sequencing. Although many experimental protocols of amplification methods have been developed, all suffer from uneven distribution of read depth across the genome after sequencing of DNA amplicons, which constrains the usage of conventional CNV calling methodologies. Here, we present SCCNV, a software tool for detecting CNVs from whole genome-amplified single cells. SCCNV is a read-depth based approach with adjustment for the WGA bias. We demonstrate its performance by analyzing data obtained with most of the single-cell amplification methods that have been employed for CNV analysis, including DOP-PCR, MDA, MALBAC, and LIANTI. SCCNV is freely available at https://github.com/biosinodx/SCCNV.
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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In multiple myeloma, abnormal plasma cells accumulate and proliferate in the bone marrow. Recently, we observed that Runx2, a bone-specific transcription factor, is highly expressed in multiple myeloma cells and is a major driver of multiple myeloma progression in bone. The primary goal of the present study was to identify Runx2-targeting miRNAs that can reduce tumor growth. Expression analysis of a panel of miRNAs in multiple myeloma patient specimens, compared with healthy control specimens, revealed that metastatic multiple myeloma cells express low levels of miR-342 and miR-363 but high levels of Runx2. Reconstituting multiple myeloma cells (CAG) with miR-342 and miR-363 reduced the abundance of Runx2 and the expression of metastasis-promoting Runx2 target genes RANKL and DKK1, and suppressed Runx2 downstream signaling pathways Akt/ß-catenin/survivin, which are required for multiple myeloma tumor progression. Intravenous injection of multiple myeloma cells (5TGM1), stably overexpressing miR-342 and miR-363 alone or together, into syngeneic C57Bl/KaLwRij mice resulted in a significant suppression of 5TGM1 cell growth, decreased osteoclasts and increased osteoblasts, and increased antitumor immunity in the bone marrow, compared with mice injected with 5TGM1 cells expressing a miR-Scramble control. In summary, these results demonstrate that enhanced expression of miR-342 and miR-363 in multiple myeloma cells inhibits Runx2 expression and multiple myeloma growth, decreases osteolysis, and enhances antitumor immunity. Thus, restoring the function of Runx2-targeting by miR-342 and miR-363 in multiple myeloma cells may afford a therapeutic benefit by preventing multiple myeloma progression.Implications: miR-342 and miR-363-mediated downregulation of Runx2 expression in multiple myeloma cells prevents multiple myeloma progression. Mol Cancer Res; 16(7); 1138-48. ©2018 AACR.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , MicroARNs/genética , Mieloma Múltiple/genética , Animales , Médula Ósea , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Osteoclastos/metabolismo , Osteoclastos/patología , Ligando RANK/genética , Transducción de SeñalRESUMEN
Inflammation-based prognostic scores, such as the glasgow prognostic score (GPS), prognostic index (PI), prognostic nutritional index (PNI), neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were related to survival in many solid tumors. Recent study showed that GPS can be used to predict outcome in diffuse large B-cell lymphoma (DLBCL). However, other inflammation related scores had not been reported and it also remained unknown which of them was the most useful to evaluate the survival in DLBCLs. In this retrospective study, a number of 252 newly diagnosed and histologically proven DLBCLs from January 2003 to December 2014 were included. The high GPS, high PI, high NLR, high PLR and low PNI were all associated with poor overall survival (p < 0.05) and event-free survival (p < 0.05) in univariate analysis. Multivariate analysis indicated that GPS (HR = 1.781, 95% CI = 1.065-2.979, p = 0.028) remained an independent prognostic predictor in DLBCL. The c-index of GPS (0.735, 95% CI = 0.645-0.824) was greater than that of PI (0.710, 95% CI = 0.621-0.799, p = 0.602), PNI (0.600, 95% CI = 0.517-0.683, p = 0.001), PLR (0.599, 95% CI = 0.510-0.689, p = 0.029) and NLR (0.572, 95% CI = 0.503-0.642, p = 0.005) by Harrell's concordance index. Especially in DLBCLs treated with R-CHOP, GPS still remained the most powerful prognostic score when comparing with others (p = 0.001 and p < 0.001, respectively for OS and EFS). In conclusion, it is indicated that inflammation-based prognostic scores such as GPS, PI, NLR, PNI and PLR all could be used to predict the outcome of DLBCLs. Among them, GPS is the most powerful indicator in predicting survival in DLBCLs, even in the rituximab era.
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The international staging system (ISS), based on serum beta-2 microglobulin and albumin, is used to predict survival in multiple myeloma, but its prognostic significance in diffuse large B-cell lymphoma (DLBCL) remains unknown. Herein, we retrospectively analyzed 215 de novo DLBCL patients. According to ISS, there were 90 of 215 (41.9%) patients in stage I, 98 of 215 (45.6%) in stage II and 27 of 215 (12.6%) in stage III group. Patients with ISS stage II/III showed shorter overall survival (OS) and event free survival (EFS) than those with stage I treated with R-CHOP (p = 0.012 and p = 0.043, respectively), but not those treated with CHOP regimen (p > 0.05). Multivariable analysis revealed that ISS, independent of IPI, indicated different survival in both OS (HR, 5.690; 95% CI, 1.270-25.495, p = 0.023) and EFS (HR, 2.116; 95% CI, 1.005-4.455, p = 0.049) in DLBCL patients treated with R-CHOP. ISS could identify patients with better outcome in intermediate-high/high IPI risk patients (p < 0.05). Our data suggests that advanced ISS stage is associated with inferior outcome in DLBCL patients treated with R-CHOP. ISS could identify a subgroup of DLBCL patients with superior outcome from high IPI risk patients, which may help to avoid intensive therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Medición de Riesgo , Rituximab , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
The germline mutation rate has been extensively studied and has been found to vary greatly between species, but much less is known about the somatic mutation rate in multicellular organisms, which remains very difficult to determine. Here, we present data on somatic mutation rates in mice and humans, obtained by sequencing single cells and clones derived from primary fibroblasts, which allows us to make the first direct comparison with germline mutation rates in these two species. The results indicate that the somatic mutation rate is almost two orders of magnitude higher than the germline mutation rate and that both mutation rates are significantly higher in mice than in humans. Our findings demonstrate both the privileged status of germline genome integrity and species-specific differences in genome maintenance.
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Mutación de Línea Germinal/genética , Tasa de Mutación , Animales , Niño , Genoma , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Ratones Endogámicos C57BLRESUMEN
Prognostic nutritional index (PNI), based on serum albumin concentration and the absolute peripheral lymphocyte count, has been used to predict survival in various tumors. Whether PNI can predict prognosis in patients with diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 253 patients with newly diagnosed DLBCL in the present study. The PNI was calculated as: albumin (g/L) + 5 × total lymphocyte count × 10(9)/L. All patients were divided in low and high groups according to the analysis of receiver operating characteristic (ROC) curve. Low PNI was associated with more unfavorable clinical features (p < 0.05). Patients with low PNI tended to have worse event-free survival (EFS) and overall survival (OS) (EFS, p = 0.001; OS, p < 0.001). For patients treated with R-CHOP, PNI proved to be predictive for survival (EFS, p = 0.001; OS, p < 0.001), while no significant effect was found in DLBCL patients who received CHOP chemotherapy (EFS, p = 0.496; OS, p = 0.125). Multivariate analysis showed that low PNI is an independent adverse predictor of OS and EFS, especially in DLBCL patients treated with R-CHOP. In conclusion, this study suggests that PNI is an effective prognostic factor in DLBCL patients treated with R-CHOP.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico , Evaluación Nutricional , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Recuento de Linfocitos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Rituximab , Albúmina Sérica/análisis , Tasa de Supervivencia , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To analyze the coagulation function and relevant factors of adults patients with acute lymphoblastic leukemia treated with pegasparase (PEG-ASP) or L-asaraginase (L-ASP). METHODS: The clinical features of 153 patients with acute lymphoblastic leukemia (ALL) received L-ASP or PEG-ASP in our hospital from January 2010 to January 2015 year were analyzed retrospectively. Among 153 patients, 108 patients received L-ASP treatment and 45 patients received PEG-ASP treatment. The change of coagulation function and the incidence of complications of 2 treated groups were compared, and the influence of differenent using time of L-ASP on above mentioned factors were analyzed. RESULTS: The age, sex, white blood cell count (WBC) at diagnosis, subtype and risk factors of disease, total effective rate and complication rates showed no significant difference in the 2 groups (P > 0.05). The total infusion of fresh frozen plasma (FFP), cryoprecipitate and fibrinogen (FIB) also showed no significant difference (P = 0.12, 0.65, 0.09). FIB levels decreased slower after treatment of PEG-ASP (9.49 vs 6.90) (P = 0.000) than that after treatment of L-ASP. When L-ASP used at interval, FIB level decreased slower than that of continuous use. However, the risk of bleeding is higher when used at interval early (P = 0.01, 0.013). CONCLUSION: Using PEG-ASP can better monitor the coagulation function than L-ASP. L-ASP used at interval can monitor the coagulation function easily, but its early use may cause an increased incidence of complications.
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Antineoplásicos/uso terapéutico , Asparaginasa/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Polietilenglicoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adulto , Fibrinógeno/análisis , Hemorragia , Humanos , Recuento de Leucocitos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The prognostic value of CD30 expression in diffuse large B-cell lymphoma (DLBCL)remains controversial. Herein, we performed this retrospective study to investigate the clinical and prognostic significance of CD30 expression in patients with DLBCL.Among all the 146 patients, the expression of CD30 was observed in 23 cases (15.7%).The DLBCL patients with CD30 expression showed more likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell-like (Non-GCB) DLBCL, BCL-2 and Ki-67 overexpression (p<0.05). Patients with CD30 expression showed significantly poor overall and event-free survival compared with CD30 negative patients(p = 0.031 and 0.041, respectively), especially those with the high intermediate/high-risk international prognostic index (IPI)(p = 0.001 and 0.007, respectively). The prognostic value of CD30 expression retained in DLBCL patients treated with either CHOP (cyclophosphamide, doxorubicin, vincristine,prednisone) or R-CHOP(rituximab+CHOP). The multivariate analysis revealed that the expression of CD30 remained an unfavorable factor for both overall and event-free survival (p = 0.001 and 0.002, respectively). In conclusion, these data suggest that CD30 is expressed predominantly in Non-GCBDLBCL. The expression of CD30 implied poor outcome in DLBCL patients treated with either CHOP or R-CHOP, especially those with the high intermediate/high-risk IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical interest.