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1.
Carbohydr Polym ; 224: 115208, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472869

RESUMO

Salecan polysaccharide produced by Agrobacterium sp. ZX09 is an attractive biopolymer to construct hydrogel scaffolds for cell culture. However, some limitations such as poor mechanical performance, complicated fabrication process and slow gelation times still exist in the biomedical applications of microbial-based salecan polysaccharide hydrogels. Here, a series of polysaccharide hydrogels composed of salecan and agarose with adjustable structural properties are designed. The resultant hybrid salecan/agarose hydrogels exhibit controllable physical and chemical properties including thermal stability, water uptake, mechanical strength and microarchitecture, which can be readily realized with minimum change of the polysaccharide content. Furthermore, cytotoxicity assays reveal that the designed composite hydrogels are non-toxic. More importantly, these hydrogels support cell survival, proliferation, and migration. Together, this work opens up a new avenue to build polysaccharide hydrogel platforms for tissue engineering.

3.
Br J Anaesth ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31383364

RESUMO

BACKGROUND: Nerve growth factor (NGF) has been implicated in hyperalgesia by sensitising nociceptors. A role for NGF in modulating myocardial injury through ischaemic nociceptive signalling is plausible. We examined whether inhibition of spinal NGF attenuates myocardial ischaemia-reperfusion injury and explored the underlying mechanisms. METHODS: In adult rats, lentivirus-mediated short-hairpin RNA targeted at reducing NGF gene expression (NGF-shRNA) or a transient receptor potential vanilloid 1 (TRPV1) antagonist (capsazepine) was injected intrathecally before myocardial ischaemia-reperfusion. Infarct size (expressed as the ratio of area at risk) and risk of arrhythmias were quantified. Whole-cell clamp patch electrophysiology was used to record capsaicin currents in primary dorsal root ganglion neurones. The co-expression of substance P (SP) and calcitonin gene-related peptide (CGRP), plus activation of TRPV1, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) were also quantified. RESULTS: NGF levels increased by 2.95 (0.34)-fold in dorsal root ganglion and 2.12 (0.27)-fold in spinal cord after myocardial ischaemia-reperfusion injury. Intrathecal injection of NGF-shRNA reduced infarct area at risk from 0.58 (0.02) to 0.37 (0.02) (P<0.01) and reduced arrhythmia score from 3.67 (0.33) to 1.67 (0.33) (P<0.01). Intrathecal capsazepine was similarly cardioprotective. NGF-shRNA suppressed expression of SP/CGRP and activation of Akt/ERK and TRPV1 in spinal cord. NGF increased capsaicin current amplitude from 144 (42) to 840 (132) pA (P<0.05), which was blocked by the TRPV1 antagonist 5'-iodoresiniferatoxin. Exogenous NGF enhanced capsaicin-induced Akt/ERK and TRPV1 activation in PC12 neuroendocrine tumour cells in culture. CONCLUSIONS: Spinal NGF contributes to myocardial ischaemia-reperfusion injury by mediating nociceptive signal transmission.

4.
Opt Lett ; 44(17): 4291-4294, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465385

RESUMO

Two-photon polymerization (TPP) based on laser direct writing is currently one of the most prevailing 3D micro/nano fabrication techniques. Nanomaterials can be doped in resins and assembled by TPP for developing advanced 3D functional devices. However, there lacks an effective visualization tool to determine the distribution and orientation of the nanomaterials as-doped in the composite resins. Herein, we present a nondestructive, in situ, and rapid characterization method to determine the orientation and distribution of the nanomaterials within cured resins using polarized second-harmonic generation (p-SHG). The directional assembly of the ZnO nanowires within micro/nanostructures fabricated by TPP is, for the first time to the best of our knowledge, characterized by p-SHG optical microscopy with a fast imaging speed by two orders of magnitude higher than that of the Raman mapping technique. Our method opens a window for nondestructive, rapid, in situ, and polarization-resolved characterization of functional devices made by TPP micro/nanofabrication.

5.
Chem Commun (Camb) ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469150

RESUMO

N/O self-doped hollow carbon nanorods (HCNs) with micro/mesoporous walls are fabricated based on a new deep-eutectic-solvent that serves as an all-in-one precursor, self-template, and self-dopant agent. The carbon-based supercapacitor using an ionic liquid electrolyte exhibits a high energy density of 116.5 W h kg-1 with excellent long-term cycling performance.

6.
J Pineal Res ; : e12607, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469445

RESUMO

Metabolic adaptations are emerging hallmarks of cancer progression and cellular transformation. Clear cell renal cell carcinoma (ccRCC) is a metabolic disease defined histologically by lipid accumulation and lipid storage, which promote tumor cell survival; however, the significance of eliminating the lipid remains unclear. Here, we demonstrate that melatonin activates transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1A (PGC1A) and uncoupling protein 1 (UCP1)-dependent lipid autophagy and a lipid browning program to elicit a catabolic state called "tumor slimming", thus suppressing tumor progression. Metabolic co-regulator data analysis revealed that PGC1A expression was decreased in ccRCC tissues versus normal tissues, and poor patient outcome was associated with lower expression of PGC1A in The Cancer Genome Atlas (TCGA-KIRC). PGC1A was downregulated in ccRCC and associated with disease progression. Restoration of PGC1A expression by melatonin in ccRCC cells significantly repressed tumor progression and eliminated the abnormal lipid deposits. Furthermore, a phenomenon called "tumor slimming" was observed, in which tumor cell volume was reduced and lipid droplets transformed into tiny pieces. Additional studies indicated that melatonin promoted "tumor slimming" and suppressed ccRCC progression through PGC1A/UCP1-mediated autophagy and lipid browning. During this process, autophagy and lipid browning eliminate lipid deposits without providing energy. These studies demonstrate that the novel "tumor slimming" pathway mediated by melatonin/PGC1A/UCP1 exhibits prognostic potential in ccRCC, thus revealing the significance of monitoring and manipulating this pathway for cancer therapy. This article is protected by copyright. All rights reserved.

7.
Mol Cancer ; 18(1): 128, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443694

RESUMO

Genetic instability of tumor cells often leads to the occurrence of a large number of mutations, and expression of non-synonymous mutations can produce tumor-specific antigens called neoantigens. Neoantigens are highly immunogenic as they are not expressed in normal tissues. They can activate CD4+ and CD8+ T cells to generate immune response and have the potential to become new targets of tumor immunotherapy. The development of bioinformatics technology has accelerated the identification of neoantigens. The combination of different algorithms to identify and predict the affinity of neoantigens to major histocompatibility complexes (MHCs) or the immunogenicity of neoantigens is mainly based on the whole-exome sequencing technology. Tumor vaccines targeting neoantigens mainly include nucleic acid, dendritic cell (DC)-based, tumor cell, and synthetic long peptide (SLP) vaccines. The combination with immune checkpoint inhibition therapy or radiotherapy and chemotherapy might achieve better therapeutic effects. Currently, several clinical trials have demonstrated the safety and efficacy of these vaccines. Further development of sequencing technologies and bioinformatics algorithms, as well as an improvement in our understanding of the mechanisms underlying tumor development, will expand the application of neoantigen vaccines in the future.

8.
Mol Cell Biochem ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432387

RESUMO

Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators in human cancer. LINC01082 was expressed as decreased in colon cancer by previous lncRNA-seq result and TCGA database, however, the role and function of LINC0182 is not clear in colon cancer. Here, we aimed to explore the role of LINC01082 in colon cancer for exploring the etiopathogenesis of colon cancer. RT-qPCR for LINC01082 expression in tissues (colon cancer vs. their matched adjacent non-cancerous tissues, ANT, n = 39) and cells (colon cancer cells vs. normal colon cells, n = 4) were performed. CCK-8 assay for proliferation of colon cancer, Transwell assay for migration and invasion were carried out in sw480 and sw620 cells. The results revealed that LINC01082 was significantly decreased in tissues and cell lines of colon cancer. Overexpressed LINC01082 significantly suppressed the proliferation ability of colon cancer cells. The migration and invasion of colon cancer cells were also suppressed after LINC01082 overexpression. These findings demonstrated that LINC01082 may act in suppressing the incidence and development of colon cancer via suppressing cell proliferation, migration and invasion, indicating that LINC01082 may act as a new tumor suppressor and may be a promising therapy target for colon cancer.

9.
FASEB J ; : fj201802416RR, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408612

RESUMO

The apelin receptor (APLNR) is a GPCR involved in many pathophysiological processes; however, the correlation between APLNR expression and nasopharyngeal carcinoma (NPC) has not been reported. In this study, we used cDNA microarray data to determine APLNR expression levels in NPC tissues. We found that APLNR expression was reduced in NPC tissues compared with noncancerous nasopharyngeal epithelial tissues. Subsequently, a large-scale sample of 1015 tissues was used to validate this discovery and explore the relationship between APLNR expression and prognosis of NPC. Expression levels of APLNR in NPC tissues were indeed down-regulated. Furthermore, positive expression of APLNR in NPC predicted a better prognosis (disease-free survival: P = 0.001; overall survival: P < 0.001). Moreover, ingenuity pathway analysis revealed that an indirect interaction existed between APLNR and retinoic acid (RA) in the cancer regulatory network. Consistently, after treatment with all-trans-RA (ATRA), we found that APLNR was significantly up-regulated in NPC cell lines (5-8F and HNE1), and proliferation of NPC cells was inhibited. Cell cycle arrest occurred in the G0/G1 phase. In contrast, knockdown of APLNR diminished ATRA-induced growth inhibition of NPC cells. In addition, we surprisingly found that APLNR also played an important role in migration and invasion of NPC. Wound-healing and Transwell assays revealed that APLNR overexpression led to reduced migratory and invasive properties in 2 NPC cell lines. Western blot results revealed that hallmarks of epithelial-mesenchymal transition (EMT) were altered as well, suggesting that APLNR was capable of inhibiting EMT in NPC cells. Our study further demonstrated that low expression of APLNR promoted EMT in NPC cells by activating the PI3K-protein kinase B-mammalian target of rapamycin signaling pathway. Taken together, our data suggest that APLNR could potentially predict prognosis for patients with NPC and inhibit proliferation, migration, invasion, and EMT in nasopharyngeal cancer cells.-Liu, Y., Liu, Q., Chen, S., Liu, Y., Huang, Y., Chen, P., Li, X., Gao, G., Xu, K., Fan, S., Zeng, Z., Xiong, W., Tan, M., Li, G., Zhang, W. APLNR is involved in ATRA-induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K-Akt-mTOR signaling.

10.
Eur Spine J ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31410620

RESUMO

PURPOSE: Multivariate analysis of T2-weighted signal, diffusion ADC, and DKI parameters and tractography were used to differentiate chronic non-specific low back pain (CLBP) patients and asymptomatic controls (AC). METHODS: A total of 30 patients with CLBP and 23 AC underwent diffusion kurtosis imaging (DKI) of lumbar spine with a 3T MRI scanner to get the ADC values and seven parameters of DKI in the nucleus pulposus (NP) of the intervertebral disc. The tractography and the tract-related parameters as other parameters were also generated to indicate the intactness of annulus fibrosus (AF). T2-grades of the discs were also quantified based on an eight-grade degeneration grading system. ADC and T2-grades were compared with DKI parameters for the differentiation of CLBP and AC groups. RESULTS: There was no difference in the T2 grades, ADC value, and multiple parameters in DKI of NP between CLBP and AC groups (P > 0.05). The average FA values in NP in AC group were found significantly higher than in the CLBP group (P < 0.05). The scores for the intactness of AF of the intervertebral discs were significantly different in CLBP and AC groups, with 90% of sensitivity and 70% specificity (P < 0.05). Additionally, there were significantly differences in the length and volume values of the AF in CLBP and AC groups (P < 0.05). CONCLUSION: DKI is a good noninvasive method, and it might help to differentiate CLBP from AC. Particularly, the continuation of DKI tractography reflects the presence of annulus fibrosus fissures, an important character in the generation of the low back pain. These slides can be retrieved under Electronic Supplementary Material.

11.
Ying Yong Sheng Tai Xue Bao ; 30(7): 2211-2217, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31418223

RESUMO

Previous studies on negative air ion (NAI), an important index for evaluating atmospheric quality, has been focused on field observation, and less on NAI under controlled condition. In this study, the NAI concentrations of different individual abundance of Liquidambar formosana and Taxus wallichiana were continuously monitored under the same climatic conditions in Hushan Experimental Base of Qianjiangyuan Forest Ecosystem Research Station, Zhejiang Province from September to October 2018. Changes of NAI concentration were monitored under different levels of air temperature and relative humidity to explore the effects of forest vegetation and meteorological factors on NAI. The results showed that both species significantly increased the NAI concentration. Plant abundance was positively correlated with the NAI concentration, and the relationship between them fitted the quadratic function with the plant abundance ranging from 0 to 50. The fitting equations for L. formosana and T. wallichiana were as follows: y=-0.0484x2+4.7005x+345.7 (R2=0.62), y=-0.0207x2+1.9189x+365.91 (R2=0.34). There was a significant positive correlation between NAI concentration and air temperature in the range of 5-30 ℃ with a fitting equation of y=0.4139x2-9.2229x+89.919 (R2=0.92). The NAI concentration and the relative humidity of air in the range of 56%-87% were positively correlated with a fitting equation of y=3.6508e0.0526x(R2=0.94).


Assuntos
Ecossistema , Conceitos Meteorológicos , Temperatura Ambiente , Umidade , Íons
12.
Adv Exp Med Biol ; 1165: 585-604, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399986

RESUMO

Oxidative stress results from the disruption of the redox system marked by a notable overproduction of reactive oxygen species. There are four major sources of reactive oxygen species, including NADPH oxidases, mitochondria, nitric oxide synthases, and xanthine oxidases. It is well known that renal abnormalities trigger the production of reactive oxygen species by diverse mechanisms under various pathologic stimuli, such as acute kidney injury, chronic kidney disease, nephrotic syndrome, and metabolic disturbances. Mutually, accumulating evidences have identified that oxidative stress plays an essential role in tubulointerstitial fibrosis by myofibroblast activation as well as in glomerulosclerosis by mesangial sclerosis, podocyte abnormality, and parietal epithelial cell injury. Given the involvement of oxidative stress in renal fibrosis, therapies targeting oxidative stress seem promising in renal fibrosis management. In this review, we sketch the updated knowledge of the mechanisms of oxidative stress generation during renal diseases, the pathogenic processes of oxidative stress elicited renal fibrosis and treatments targeting oxidative stress during tubulointerstitial fibrosis and glomerulosclerosis.

13.
Metab Eng ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31401243

RESUMO

Metabolic engineering is a critical biotechnological approach in addressing global energy and environment challenges. Most engineering efforts, however, consist of laborious and inefficient trial-and-error of target pathways, due in part to the lack of methodologies that can comprehensively assess pathway properties in thermodynamics and kinetics. Metabolic engineering can benefit from computational tools that evaluate feasibility, expense and stability of non-natural metabolic pathways. Such tools can also help us understand natural pathways and their regulation at systems level. Here we introduce a computational toolbox, PathParser, which, for the first time, integrates multiple important functions for pathway analysis including thermodynamics analysis, kinetics-based protein cost optimization and robustness analysis. Specifically, PathParser enables optimization of the driving force of a pathway by minimizing the Gibbs free energy of least thermodynamically favorable reaction. In addition, based on reaction thermodynamics and enzyme kinetics, it can compute the minimal enzyme protein cost that supports metabolic flux, and evaluate pathway stability and flux in response to enzyme concentration perturbations. In a demo analysis of the Calvin-Benson-Bassham cycle and photorespiration pathway in the model cyanobacterium Synechocystis PCC 6803, the computation results are corroborated by experimental proteomics data as well as metabolic engineering outcomes. This toolbox may have broad application in metabolic engineering and systems biology in other microbial systems.

14.
Chemistry ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415126

RESUMO

The controlled formation of complex and functional 1-, 2-, and 3-D hierarchical assemblies from molecular building blocks represents a key current challenge. Herein, we report the use of a seeded growth approach for a series of perylenediimide-based molecules (PDIs 1 - 4) to access otherwise inaccessible self-assembly pathways that yield complex hierarchical structures. The key to the new approach is to use hetero-seeds which possess a different composition and morphology from that of the molecular building block. For example, a nanotube seed (from PDI 3) and a microribbon seed (from PDI 4) were found to initiate different self-assembly pathways for PDI 1, which normally assembles to yield nanocoils. This led to the formation of unprecedented 3D scroll-like and scarf-like hierarchical nanostructures, respectively. Also, the hetero-seeds from PDI 3 initiate hidden self-assembly pathways of PDI 2 to generate 1D tubular heterojunctions. Significantly, this new strategy offers new opportunities to create emergent and functional hierarchical and complex structures from small molecule precursors.

15.
iScience ; 19: 634-646, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31450193

RESUMO

Hyperekplexia disease is usually caused by naturally occurring point mutations in glycine receptors (GlyRs). However, the γ-aminobutyric acid type A receptor (GABAAR) seems to be also involved regarding the therapeutic basis for hyperekplexia using benzodiazepines, which target GABAARs but not GlyRs. Here, we show that the function of GABAARs was significantly impaired in the hypoglossal nucleus of hyperekplexic transgenic mice. Such impairment appeared to be mediated by interaction between GABAAR and mutant GlyR. The GABAAR dysfunction was caused only by mutant GlyR consisting of homomeric α1 subunits, which locate primarily at pre- and extra-synaptic sites. In addition, the rescue effects of diazepam were attenuated by Xli-093, which specifically blocked diazepam-induced potentiation on α5-containing GABAAR, a major form of pre- and extra-synaptic GABAAR in the brainstem. Thus, our results suggest that the pre- and extra-synaptic GABAARs could be a potential therapeutic target for hyperekplexia disease caused by GlyR mutations.

16.
Mol Genet Genomic Med ; : e903, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454181

RESUMO

BACKGROUND: Studies have identified that the telomerase reverse transcriptase (TERT) gene polymorphism rs10069690 (C>T) is associated with cancer risk, but the results remain inconclusive. METHODS: To provide a more precise estimation of the relationship, we performed a meta-analysis of 45 published studies including 329,035 cases and 730,940 controls. We conducted a search in PubMed, Google Scholar and Web of Science to select studies on the association between rs10069690 and cancer risk. Stratification by ethnicity, cancer type, cancers' classification, source of control, sample size, and genotype method was used to explore the source of heterogeneity. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated using random effects models. Sensitivity, publication bias, false-positive report probability (FPRP) and statistical power were also assessed. RESULTS: The result demonstrated that rs10069690 was significantly associated with an increased risk of cancer overall (OR = 1.09, 95% CI: 1.06-1.12, p < .001) under the allele model. Stratification analysis revealed an increased cancer risk in subgroups of breast cancer, ovarian cancer, lung cancer, thyroid cancer, and renal cell carcinoma (RCC). However, a significantly decreased association was observed in pancreatic cancer in the European population (OR = 0.93,95% CI: 0.87-0.99, p = .031). In the subgroup analysis based on cancer type, no significant association was found in prostate cancer, leukemia, colorectal cancer and glioma. CONCLUSIONS: This meta-analysis suggested that the TERT rs10069690 polymorphism may be a risk factor for cancer, especially breast cancer, ovarian cancer, lung cancer, thyroid cancer, and RCC. Further functional studies are warranted to reveal the role of the polymorphism in carcinogenesis.

17.
Ann Clin Lab Sci ; 49(3): 368-371, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31308037

RESUMO

OBJECTIVE: This study aims to investigate the changes in CD3+, CD4+ and CD8+ expression in cells in peripheral blood of silicosis patients, and observe the immunoregulatory effect of thymalfasin. METHODS: A total of 80 silicosis patients were enrolled in the study, randomly divided into two groups: treatment group and control group (n=40, each group). In addition, 40 healthy adults, who underwent physical examinations in our hospital, were enrolled into the health examination group. Patients in the control group and treatment group were given anti-infection treatment, according to their conditions. Patients in the treatment group additionally received thymalfasin. Then, the number of peripheral blood T lymphocyte subsets in subjects in all three groups before and after treatment was measured. RESULTS: (1) Before treatment, CD3+, CD4+ and CD8+ levels in cells were significantly lower in the treatment group and control group than in the health examination group, and the differences were statistically significant (P<0.05). (2) In the treatment group, the number of CD4+ cells in peripheral blood was significantly higher after one week of treatment, when compared to that before treatment, and the difference was statistically significant (P<0.05). CONCLUSION: In silicosis patients, CD3+, CD4+ and CD8+ cells in peripheral blood are decreased, and thymalfasin can significantly increase CD4+ cells in peripheral blood of silicosis patients.

18.
Cell Mol Life Sci ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31309249

RESUMO

Numerous studies have shown that non-coding RNAs play crucial roles in the development and progression of various tumor cells. Plasmacytoma variant translocation 1 (PVT1) mainly encodes a long non-coding RNA (lncRNA) and is located on chromosome 8q24.21, which constitutes a fragile site for genetic aberrations. PVT1 is well-known for its interaction with its neighbor MYC, which is a qualified oncogene that plays a vital role in tumorigenesis. In the past several decades, increasing attention has been paid to the interaction mechanism between PVT1 and MYC, which will benefit the clinical treatment and prognosis of patients. In this review, we summarize the coamplification of PVT1 and MYC in cancer, the positive feedback mechanism, and the latest promoter competition mechanism of PVT1 and MYC, as well as how PVT1 participates in the downstream signaling pathway of c-Myc by regulating key molecules. We also briefly describe the treatment prospects and research directions of PVT1 and MYC.

19.
Chin Med J (Engl) ; 132(15): 1773-1779, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31335474

RESUMO

BACKGROUND: Cascade analysis is an effective method to analyze the processing data of an event, such as a provided service or a series of examinations. This study aimed to develop a primary cervical cancer screening cascade in China to promote the quality of the screening process. METHODS: We designed a cervical cancer screening cascade in China according to the program flow chart. It had three stages, each with two steps and one result. Data from 117,522 women aged 35 to 64 years in the Rural Cervical Cancer Surveillance Project from January 1, 2014, to December 31, 2014, were collected to analyze the main results of the cascade. The data and proportion are used to describe the follow-up of cervical cancer and pre-cancer detection rate. RESULTS: In 2014, 117,522 (80.94% of all cases reported by the Rural Cervical Cancer Surveillance Project) women aged 35 to 64 years had not received cervical cytology in the previous 3 years. The pre-cancer and cancer detection rates were 256.12/100,000 and 16.16/100,000, respectively. A total of 3031 cases failed to follow-up through the screening process, and 1189, 1555, and 287 cases were lost at cervical cytology, colposcopy, and histopathological screening stages, respectively. The estimated cases of pre-cancer and cancer cases would have been 544 and 34, respectively, and the estimated detection rates of pre-cancer and cancer would have been 462.89/100,000 and 28.93/100,000, respectively. CONCLUSION: In order to increase the detection rate of cervical cancer, cervical cancer screening staff should focus on increasing the rate of follow-up of those who are positive for cervical cancer screening (ie, those with positive cytology results), especially for the 40 to 44 years age range.

20.
Am J Hematol ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321805

RESUMO

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD- CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD- CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD- CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

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