Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.714
Filtrar
1.
Carcinogenesis ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31587040

RESUMO

Previous research suggests that Far Upstream-element Binding Protein 1 (FUBP1)plays an important role in various tumors including Hepatocellular carcinoma (HCC). However, the role of FUBP1 in liver cancer remains controversial, and the regulatory pathway by FUBP1 awaits to be determined. This study aims to identify the role of FUBP1 in hepatocellular carcinoma progression. Our result shows that high level of FUBP1 expression in HCC predicts poor prognosis after surgery. Overexpression of FUBP1 promotes HCC proliferation, invasion and metastasis by activating Transforming Growth Gactor-ß(TGF-ß)/Smad pathway and enhancing Epithelial-Mesenchymal Transition (EMT) in vitro and in vivo. Inhibitor of Thrombospondin-1 (LSKL)could inhibit HCC proliferation and invasion in vitro and in vivo by blocking the activation of TGF-ß/Smad pathway mediated by Thrombospondin-1 (THBS1). Our study identified the critical role of FUBP1-THBS1-TGF-ß signaling axis in HCC and provides potentially new therapeutic modalities in HCC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31578860

RESUMO

In this work, nanoplasmonic enhanced α-Ga2O3 solar-blind photodetectors with interdigital structure were fabricated on sapphire. By introducing Al nanoparticles (NPs) onto the device surface, the photodetector obtained a significant increase in responsivity at solar-blind region, and the response peak located at 244 nm reached 3.36 A/W under applied voltage of 5 V. Compared with the responsivity at 320 nm, the response ratio exceeds 240, demonstrating a superior solar-blind cut-off edge. It also presents that the photocurrent was dramatically increased under the 254 nm ultraviolet irradiation for the enhanced device while the dark current remains below 1 pA at 20 V. To explicitly elucidate the enhancement effects by Al NPs under ultraviolet illumination, Kelvin probe force microscopy was employed and directly revealed the physical mechanism of surface plasmon oscillation which promoted the formation of localized electric fields on α-Ga2O3. In addition, we illustrated the effects of interdigital spacing on device performances through experimental measurements and theoretical calculations. These results not only provide direct evidences for Al nanoplasmonic enhancement on α-Ga2O3 device, but also facilitate design and fabrication of solar-blind photodetectors.

3.
CNS Neurosci Ther ; 25(10): 1113-1125, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31578825

RESUMO

The predilection site of intracerebral hemorrhage (ICH) is in the basal ganglia, which is rich in white matter (WM) fiber bundles, such as cerebrospinal tract in the internal capsule. ICH induced damage to this area can easily lead to severe neurological dysfunction and affects the prognosis and quality of life of patients. At present, the pathophysiological mechanisms of white matter injury (WMI) after ICH have attracted researchers' attention, but studies on the repair and recovery mechanisms and therapy strategies remain rare. In this review, we mainly summarized the WM recovery and treatment strategies after ICH by updating the WMI-related content by reviewing the latest researches and proposing the bottleneck of the current research.

4.
Genes (Basel) ; 10(10)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581635

RESUMO

Root system plays an essential role in water and nutrient acquisition in plants. Understanding the genetic basis of root development will be beneficial for breeding new cultivars with efficient root system to enhance resource use efficiency in maize. Here, the natural variation of 13 root and 3 shoot traits was evaluated in 297 maize inbred lines and genome-wide association mapping was conducted to identify SNPs associated with target traits. All measured traits exhibited 2.02- to 21.36-fold variations. A total of 34 quantitative trait loci (QTLs) were detected for 13 traits, and each individual QTL explained 5.7% to 15.9% of the phenotypic variance. Three pleiotropic QTLs involving five root traits were identified; SNP_2_104416607 was associated with lateral root length (LRL), root surface area (RA), root length between 0 and 0.5mm in diameter (RL005), and total root length (TRL); SNP_2_184016997 was associated with RV and RA, and SNP_4_168917747 was associated with LRL, RA and TRL. The expression levels of candidate genes in root QTLs were evaluated by RNA-seq among three long-root lines and three short-root lines. A total of five genes that showed differential expression between the long- and short-root lines were identified as promising candidate genes for the target traits. These QTLs and the potential candidate genes are important source data to understand root development and genetic improvement of root traits in maize.

5.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3246-3252, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602879

RESUMO

Inula japonica was used as the research object, "3414" fertilization experiment were conducted to study the effects of nitrogen,phosphorus and potassium formula fertilizer on the growth and chemical composition content of I. japonica. The characteristics of fertilizer requirement were preliminarily revealed and the study provided fertilization guidance for artificial cultivation of I. japonica. The results showed that different nitrogen,phosphorus and potassium formula fertilizers had significant effects on plant morphology,physiological and biochemical indexes,dry matter accumulation and chemical composition content. The growth indexes and chemical components of I. japonica showed an upward trend with the increase of fertilization amount,especially the nitrogen fertilizer was the most significant. The indicators were analyzed by membership function. After comprehensive evaluation,the optimal nitrogen,phosphorus and potassium formula fertilization level was N3 P2 K2,namely high level nitrogen fertilizer,medium level phosphorus fertilizer and potassium fertilizer. I. japonica is a high fertilizer demand plant,and the rational fertilization scheme is " applying nitrogen fertilizer again and applying phosphorus and potassium fertilizer properly".

6.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3711-3717, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602943

RESUMO

In this paper,the fingerprint of different varieties of chrysanthemum were established with " Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Medica" and the content of chlorogenic acid,galuteolin and 3,5-O-dicaffeoylquinic acid in 29 batches of different varieties of chrysanthemum in Futianhe town,Huangtugang town and Wuhan city were compared. At the same time,similarity evaluation and common peak clustering analysis were carried out. There were 11 common peaks in the fingerprints of 29 batches of different varieties of chrysanthemum,and the similarity ranged from 0. 802 to 0. 975. Hangju and Gongju were divided into one group by cluster analysis,and Huangju into another category. The established fingerprint method provides a basis for the identification of chrysanthemum cultivars. The content of 29 batches of chlorogenic acid was between 4. 092 and 11. 723 mg·g-1,luteolin was between 1. 010 and 11. 713 mg·g-1,and 3,5-O-dicaffeoylquinic acid was between 8. 828 and 33. 435 mg·g-1,both reach the pharmacopoeia standard,but the effective components of different varieties of chrysanthemum were quite different. Based on the contents of three active ingredients and the diversity of fingerprint peaks,the quality of the characteristic germplasm resource of local Fubaijuin Macheng is superior,and the protection of local characteristic germplasm resource should be strengthened in production.

7.
Sensors (Basel) ; 19(19)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569712

RESUMO

Automatic Identification System (AIS) data could support ship movement analysis, and maritime network construction and dynamic analysis. This study examines the global maritime network dynamics from multi-layers (bulk, container, and tanker) and multidimensional (e.g., point, link, and network) structure perspectives. A spatial-temporal framework is introduced to construct and analyze the global maritime transportation network dynamics by means of big trajectory data. Transport capacity and stability are exploited to infer spatial-temporal dynamics of system nodes and links. Maritime network structure changes and traffic flow dynamics grouping are then possible to extract. This enables the global maritime network between 2013 and 2016 to be investigated, and the differences between the countries along the 21st-century Maritime Silk Road and other countries, as well as the differences between before and after included by 21st-century Maritime Silk Road to be revealed. Study results indicate that certain countries, such as China, Singapore, Republic of Korea, Australia, and United Arab Emirates, build new corresponding shipping relationships with some ports of countries along the Silk Road and these new linkages carry significant traffic flow. The shipping dynamics exhibit interesting geographical and spatial variations. This study is meaningful to policy formulation, such as cooperation and reorientation among international ports, evaluating the adaptability of a changing traffic flow and navigation environment, and integration of the maritime economy and transportation systems.

8.
Sensors (Basel) ; 19(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480359

RESUMO

With the development of the Internet-of-Things (IoT) technology, the applications of gas sensors in the fields of smart homes, wearable devices, and smart mobile terminals have developed by leaps and bounds. In such complex sensing scenarios, the gas sensor shows the defects of cross sensitivity and low selectivity. Therefore, smart gas sensing methods have been proposed to address these issues by adding sensor arrays, signal processing, and machine learning techniques to traditional gas sensing technologies. This review introduces the reader to the overall framework of smart gas sensing technology, including three key points; gas sensor arrays made of different materials, signal processing for drift compensation and feature extraction, and gas pattern recognition including Support Vector Machine (SVM), Artificial Neural Network (ANN), and other techniques. The implementation, evaluation, and comparison of the proposed solutions in each step have been summarized covering most of the relevant recently published studies. This review also highlights the challenges facing smart gas sensing technology represented by repeatability and reusability, circuit integration and miniaturization, and real-time sensing. Besides, the proposed solutions, which show the future directions of smart gas sensing, are explored. Finally, the recommendations for smart gas sensing based on brain-like sensing are provided in this paper.

9.
J Biol Chem ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481466

RESUMO

Polyunsaturated fatty acids (PUFAs) such as α-linolenic acid (ALA, 18:3Δ9cis,12cis,15cis ) have high nutritional and industrial values. In oilseed crops, PUFAs are synthesized on phosphatidylcholine (PC) and accumulated in triacylglycerol (TAG). Therefore, exploring the mechanisms that route PC-derived PUFA to TAG is essential for understanding and improving PUFA production. The seed oil of flax (Linum usitatissimum) is enriched in ALA, and this plant has many lipid biosynthetic enzymes that prefer ALA-containing substrates. In this study, using membrane yeast two-hybrid and bimolecular fluorescence complementation assays, we probed recombinant flax transferase enzymes, previously shown to contribute to PUFA enrichment of TAG, for physical interactions with each other under in vivo conditions. We found that diacylglycerol acyltransferases, which catalyze the final reaction in acyl-CoA-dependent TAG biosynthesis, interact with the acyl-editing enzymes phosphatidylcholine: diacylglycerol cholinephosphotransferase and lysophosphatidylcholine acyltransferase. Physical interactions among the acyl-editing enzymes were also identified. These findings reveal the presence of an assembly of interacting transferases that may facilitate the channeling of PUFA from PC to TAG in flax and possibly also in other oleaginous plants that produce seeds enriched in PC-modified fatty acids.

10.
Oncol Rep ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545501

RESUMO

The minichromosome maintenance (MCM) gene family plays an essential role in DNA replication and cell cycle progression. However, MCM gene expression has not been well­studied in lung adenocarcinoma (LUAD). In the present study, the expression, prognostic value and functions of MCMs in LUAD were investigated using several databases and bioinformatic tools, including Oncomine, GEPIA, cBioPortal, CancerSEA and Kaplan­Meier plotter. It was demonstrated that the mRNA expression of MCM2, MCM4 and MCM10 were significantly increased in patients with LUAD. High mRNA expression of MCM2­5, MCM8 and MCM10 were associated with poor overall survival and progression­free survival. High MCM4 expression was associated with adverse post­progression survival. In addition, the Human Protein Atlas database showed that MCM protein expression was consistent with the mRNA expression. These results demonstrate that MCM2, MCM4 and MCM10 are potential prognostic markers and therapeutic targets for LUAD.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31473923

RESUMO

Little is known regarding the effects of environmental mercury (Hg) exposure on liver dysfunction in adolescents. We aimed to explore the association between Hg exposure and the risk of nonalcoholic fatty liver disease (NAFLD) in the adolescent population. The cross-sectional associations between blood Hg concentrations and serum alanine aminotransferase (ALT) levels, a surrogate for suspected NAFLD, were evaluated using data from adolescents (aged 12-17 years old) who participated in the National Health and Nutrition Examination Survey (NHANES), 1999-2014. A final sample of 6389 adolescents was analysed. Elevated ALT was defined as > 25 IU/L and > 22 IU/L for boys and girls ≤ 17 years old, respectively. Odds ratios (ORs) of Hg levels in association with serum ALT levels were estimated using a logistic regression after adjusting for gender, age, ethnicity, serum cotinine, body mass index, the poverty income ratio, and NHANES cycles. The median blood Hg level was 0.73 ± 0.91 µg/L amongst US adolescents. In the adjusted model, the ORs of elevated ALT levels of those in the 4th quartile were higher amongst non-Hispanic white adolescents (OR = 1.76, 95% CI 1.20, 2.59; P = 0.035) and those who were normal or underweight (OR = 1.41, 95% CI 1.08, 1.85; P = 0.020). No association was observed for the other variables. Our results indicate that the positive association between blood Hg exposure and the risk of NAFLD in US adolescents is the highest amongst non-Hispanic white and those who are normal or underweight, regardless of ethnicity. More research is necessary to confirm this association and to clarify the potential mechanisms.

12.
Foodborne Pathog Dis ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31478765

RESUMO

In the field of the detection of pathogens responsible for infectious diarrhea, multiplex nucleic acids detection technology has attracted attention due to its ability to simultaneously screen a wide range of pathogens, its simplicity to operate and a faster turnaround time. We conducted a three-center evaluation that compared the BioFire FilmArray gastrointestinal panel (FA GI) and real-time polymerase chain reaction (PCR) assays for the detection of pathogens from 462 clinical diarrhea specimens, and characterized the distribution of various pathogens that were analyzed. The sensitivity of FA GI was 100% for 13 pathogens and 93.8-98.3% for 4 pathogens, but low for Salmonella (60.5%) and adenovirus (88.9%). The sensitivity per pathogen of real-time PCR assays was lower than that observed with FA GI. The specificity of FA GI and real-time PCR assays per pathogen was greater than 94.5% and 99%, respectively. FA GI and real-time PCR assays detected ≥1 pathogen in 339 (73.4%) and 297 (64.3%) samples, respectively, and 324 (70.1%) samples were considered as positive according to the reference standard. Multiple pathogens were detected in 37.2% and 24.9% of samples by FA GI and real-time PCR assays, respectively. Norovirus GI/GII and Campylobacter were less associated with coinfections. The positive rates of some pathogens varied among the three regions of China. Molecular methods can help squickly identify the cause of diarrhea and provide valuable information for early diagnosis and optimal patient therapy.

13.
Arch Insect Biochem Physiol ; : e21626, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31562754

RESUMO

Insects can produce various antimicrobial peptides (AMPs) upon immune stimulation. One class of AMPs are characterized by their high proline content in certain fragments. They are generally called proline-rich antimicrobial peptides (PrAMPs). We previously reported the characterization of Spodoptera litura lebocin-1 (SlLeb-1), a PrAMP proprotein. Preliminary studies with synthetic polypeptides showed that among the four deductive active fragments, the C-terminal fragment SlLeb-1 (124-158) showed strong antibacterial activities. Here, we further characterized the antibacterial and antifungal activities of 124-158 and its four subfragments: 124-155, 124-149, 127-158, and 135-158. Only 124-158 and 127-158 could agglutinate bacteria, while 124-158 and four subfragments all could agglutinate Beauveria bassiana spores. Confocal microscopy showed that fluorescent peptides were located on the microbial surface. Fragment 135-158 lost activity completely against Escherichia coli and Staphylococcus aureus, and partially against Bacillus subtilis. Only 124-149 showed low activity against Serratia marcescens. Negative staining, transmission, and scanning electron microscopy of 124-158 treated bacteria showed different morphologies. Flow cytometry analysis of S. aureus showed that 124-158 and four subfragments changed bacterial subpopulations and caused an increase of DNA content. These results indicate that active fragments of SlLeb-1 may have diverse antimicrobial effects against different microbes. This study may provide an insight into the development of novel antimicrobial agents.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31514150

RESUMO

Deep learning has recently gained more and more popularity, because of its high accuracy and wide range of coverage. In particular, deep learning is widely used in the medical field. Because in the field of image classification and biological applications, the accuracy of deep learning is very high. Unfortunately, even under the collaborative deep learning, there is still serious risk of information leakage. Moreover, the risk of information leakage in the medical field is greater and the harm is even greater. For example, medical treatment data may be leaked to third-party organizations. When these important medical data is illegally used by for-profit organizations or obtained by criminals, it will not only lead to the disclosure of personal privacy information, but also cause serious economic losses to the victims. However, the victim cannot delete the leaked information by itself or limit the scope and use of the information that has been leaked. Therefore, the adverse effects are unimaginable. This paper mainly studies the information protection methods under GAN model attack, in order to find a better way to prevent attacks and effectively protect information.

15.
Environ Res ; 178: 108666, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31472363

RESUMO

Studies have shown that persistent organic pollutants (POPs) can have various health effects. However, little is known about the effects of multiple chemicals with possible common sources of exposure on walking speed, a proxy index reflecting lower limb neuromuscular function and physical function. We simultaneously applied multiple linear and nonlinear statistical models to explore the complex exposure-response relationship between a mixture of 22 selected POPs and walking speed. A total of 14 polychlorinated biphenyls (PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 5 polychlorinated dibenzofurans (PCDFs) were measured in the serum of participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002. Walking speed was measured during a physical examination. Linear regression (LR), least absolute shrinkage and selection operator (LASSO), and group LASSO were used to evaluate the linearity of mixtures, while restricted cubic spline (RCS) regression, random forest (RF), and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Potential confounders were adjusted in the above models. A total of 436 subjects were included in our final analysis. The results of the LR model did not identify any POP exposure that was significantly associated with walking speed. The LASSO results revealed an inverse association of one PCDD congener and two PCDF congeners with walking speed, while the group LASSO analysis identified PCDFs at the exposure level and at the group level. In the RCS analysis, two PCB congeners presented significant overall associations with walking speed. The PCB congener PCB194 showed statistically significant effects on the outcome (P = 0.01) when a permutation-based RF was used. The BKMR analysis suggested that PCBs and PCDFs (probabilities = 0.887 and 0.909, respectively) are potentially associated with walking speed. Complex statistical models, such as RCS regression, RF and BKMR models, can detect the nonlinear and nonadditive relationships between PCBs and walking speed, while LASSO and group LASSO can identify only the linear relationships between PCDFs and walking speed. Fully considering the influence of collinearity in each method during modelling can increase the comprehensiveness and reliability of conclusions in studies of multiple chemicals.

16.
Prostate ; 79(15): 1762-1766, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31497879

RESUMO

BACKGROUND: Family history (FH) of prostate cancer (PCa) in Chinese population is poorly understood. The objective of this study is to evaluate the association between FH and PCa in a Chinese biopsy cohort. METHODS: Consecutive patients who received 10 to 12 core systematic prostate biopsies from April 2013 to October 2018 in three medical centers were enrolled in this study. Demographic information and clinical information were obtained through prebiopsy questionnaire, including cancer FH, age, and total prostate-specific antigen (tPSA). RESULTS: Of 2321 patients, 83 (3.6%) were reported a FH of PCa. The positive biopsy rate in these patients was 54.2%, significantly higher than the patients without the family history of PCa (42.6%; relative risk [RR] = 1.27; P = .024). In patients with positive FH of breast cancer gene (BRCA)-related cancers (breast, ovarian, and prostate cancer, n = 154), 74 (48.1%) were diagnosed as PCa, higher than those without FH (42.7%; RR = 1.13; P = .112). Multivariate logistic regression analysis (after adjusting for age and tPSA values) showed that there was 2.1-fold increased risk of PCa in patients with positive FH of PCa (P = .005), and 1.6-fold increased risk in patients with positive FH of BRCA-related cancers (P = .019). However, there was no significant association between FH of PCa or BRCA-related cancer and high-grade PCa after adjusting age and tPSA level (P = .404 for PCa, P = 0.991 for BRCA-related cancers). CONCLUSIONS: Patients with positive FH of PCa had 2.1-fold higher risk of PCa, and patients with positive FH of BRCA-related cancers had 1.6-fold higher risk in this biopsy cohort of Chinese population. Patients with positive FH of PCa or BRCA-related cancers would have earlier age at onset of PCa.

17.
J Biomed Mater Res A ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498962

RESUMO

Platelet-rich plasma (PRP) is rich in a variety of growth factors and plays an important role in the proliferation and differentiation of mesenchymal stem cells (MSCs). It has been reported that the preparation of freeze-dried platelets (lyophilized platelets [LyPRP]) from platelets could be an effective strategy to preserve the bioactivity of platelets for a long time. In this study, the osteogenic induction effects of PRP and LyPRP on MSCs were evaluated. The rabbit arterial blood was drawing to preparation of PRP by secondary centrifugation. Whole blood was prepared by lyophilization buffer to prepare LyPRP, which were activated by chloride and their surface morphology was observed. It was observed using a scanning electron microscope that platelets were evenly distributed on the surface of PRP and LyPRP. Growth factors were slowly released from PRP and LyPRP during the first 7 days and detected by the enzyme-linked immunosorbent assay kit. Cell proliferation assays and fluoresceindiacetate/propidium iodide (FDA/PI) staining demonstrated that PRP and LyPRP could promote cell proliferation. PRP and LyPRP were also shown to promote osteogenic differentiation of MSCs in vitro by osteogenesis characteristic staining and qPCR quantitative detection of osteogenic related gene expression. Both PRP and LyPRP could promote the proliferation and osteogenic differentiation of MSCs effectively. Moreover, PRP exhibited a better osteogenic induction effect on MSC than LyPRP.

18.
J Phys Chem Lett ; 10(19): 5786-5790, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31515995

RESUMO

Predicting the thermometric performance of diverse materials will facilitate the selection and design of nanothermometers to suit complex environments and specific signal outputs while saving much time and expense. Herein we explore and unveil the thermal-coupled thermometric performance of Er3+/Yb3+ codoped in a set of host lattices via the chemical bond theory of complex crystals. The unknown B and ΔE values of the thermometry are accurately estimated by the chemical bond parameters, further deepening our cognition of the correlation between the luminescence properties of Er3+ ions and the microscopic crystal structure. This allows us to precisely forecast the thermal-coupled thermometric performance of Er3+ for varying host lattices in advance.

19.
Genes (Basel) ; 10(9)2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480272

RESUMO

ZmPGP1, involved in the polar auxin transport, has been shown to be associated with plant height, leaf angle, yield traits, and root development in maize. To explore natural variation and domestication selection of ZmPGP1, we re-sequenced the ZmPGP1 gene in 349 inbred lines, 68 landraces, and 32 teosintes. Sequence polymorphisms, nucleotide diversity, and neutral tests revealed that ZmPGP1 might be selected during domestication and improvement processes. Marker-trait association analysis in inbred lines identified 11 variants significantly associated with 4 plant architecture and 5 ear traits. SNP1473 was the most significant variant for kernel length and ear grain weight. The frequency of an increased allele T was 40.6% in teosintes, and it was enriched to 60.3% and 89.1% during maize domestication and improvement. This result revealed that ZmPGP1 may be selected in the domestication and improvement process, and significant variants could be used to develop functional markers to improve plant architecture and ear traits in maize.

20.
J Hematol Oncol ; 12(1): 88, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481121

RESUMO

BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. METHODS: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. RESULTS: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). CONCLUSIONS: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA