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1.
Artigo em Inglês | MEDLINE | ID: mdl-31487451

RESUMO

Low-density 3D ultrafine fiber assemblies obtained from direct electrospinning enable promising applications in sound absorption fields but are often hindered by their poor structure stability. Here we demonstrate an electrospun ultrafine fiber sponge with microstructure-derived reversible elasticity and high sound absorption property, which is achieved by designing a hierarchical lamellar corrugated architecture that functioned as elastic units. The obtained electrospun fiber sponge can quickly recover to the original height even under the distortion from burdens 8900 times of its weight. Particularly, the material can maintain its structural stability after 100 cycles at 60% strain. What's more, the initial hierarchical structure and hydrophobicity of the prepared materials endow them with an ultralight property (density of 6.63 mg cm-3), superior low-frequency sound absorption and excellent performance maintenance. The successful synthesis of these fascinating materials may provide new sights into the design of lightweight and efficient sound absorption materials.

2.
J Exp Clin Cancer Res ; 38(1): 345, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391118

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is the malignant tumor of the female reproductive system with the highest fatality rate. Tolerance of chemotherapeutic drugs like cisplatin (DDP) occurring in very early stage is one of the important factors of the poor prognosis of epithelial ovarian cancer. Here we aim to study the dysregulation of a particular long noncoding RNA, lncRNA GAS5, and its role in EOC progression. METHODS: The low expression of lncRNA GAS5 in EOC tissues and OC cell lines was determined by microarray analyses and Real-Time qPCR. Flow cytometer assays were used to detect cell cycle and apoptosis of OC cells. CCK8 assay were performed to investigate the DDP sensitivity of OC cells. Western blot was carried out to detect cell growth markers, apoptotic markers, PARP1, E2F4, MAPK pathway protein expression and other protein expression in OC cell lines. The binding of GAS5 and E2F4 were proved by RNA pull-down and RIP assay. The effect of E2F4 on PARP1 were determined by CHIP-qPCR assay and luciferase reporter assay. The effect of lncRNA GAS5 on OC cells was assessed in vitro and in vivo. RESULTS: By microarray (3 EOC tissues νs. 3 normal ovary tissues) and RT- qPCR (53 EOC tissues νs. 10 normal ovary tissues) we identified lncRNA GAS5 to be dramatically low expressed in EOC samples and correlated with prognosis. Compared with sensitive cell lines, GAS5 was also low expressed in DDP resistant OC cell lines, and over-expression of GAS5 significantly enhanced the sensitivity of OC cells to DDP in vivo and in vitro. Meanwhile the over-expression of GAS5 also caused OC cells G0/G1 arrest and apoptosis increase. Mechanistically, GAS5 might regulate PARP1 expression by recruiting the transcription factor E2F4 to its promoter, and then affect the MAPK pathway activity. Due to the 5'TOP structure, GAS5 could be regulated by transcription inhibitor rapamycin in OC cells. CONCLUSION: Here we explored the specific mechanisms of EOC cisplatin resistance and tumor progress due to lncRNA-GAS5, presented the GAS5-E2F4-PARP1-MAPK axis and its role in OC drug-sensitivity and progression for the first time, and the results may provide experimental basis for clinical application.

3.
Int J Toxicol ; : 1091581819864518, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342801

RESUMO

Triptolide is a major active ingredient isolated from the traditional Chinese herb Tripterygium wilfordii Hook F. However, its use in clinical practice is limited due to its severe hepatotoxicity. Autophagy, a highly conserved intracellular process, is essential for maintaining cytoplasmic homeostasis. Considering that abnormalities in autophagy are closely associated with drug-mediated hepatotoxicity, we applied human normal liver HL7702 cells to elucidate the roles of autophagy in triptolide-induced hepatotoxicity. Our study revealed that triptolide was cytotoxic to HL7702 cells. It markedly increased autophagosome formation and expression of autophagy-related proteins, namely Beclin1 and microtubule-associated protein 1 light chain 3II, and induced oxidative stress. These proautophagic effects were counteracted by pretreatment with N-acetylcysteine, a reactive oxygen species scavenger. Moreover, the pharmacological suppression of autophagy further exacerbated triptolide-elicited decrease in cell viability, increase in lactate dehydrogenase leakage, and activation of apoptosis proteases (caspase 3 and caspase 9). Our findings suggest that triptolide-induced oxidative stress consequently enhances autophagic activity, and autophagy is a cytoprotective mechanism against triptolide-induced cytotoxicity in HL7702 cells.

4.
J Craniofac Surg ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31343590

RESUMO

Conjunctival prolapse may occur following ocular, eyelid, and orbital surgeries. Conjunctival prolapse usually results as a complication of maximal levator resection or cosmetic lower eyelid blepharoplasty. Here, we describe conjunctival prolapse as an unexpected complication of frontalis muscle flap transfer for severe ptosis. On postoperative day 5, the patient experienced upper eyelid swelling after closing his eyes suddenly and standing up abruptly. The conjunctiva was reddish and ballooned up, and they protruded over the eyelids. Conjunctival prolapse persisted until postoperative day 8. The patient and surgeon were concerned that this complication would affect ptosis correction and surgical outcome. U-shaped fixations were placed to suture and force the prolapsed conjunctiva back to their normal anatomical positions. At postoperative 6 months, the patient had not experienced additional issues, and he was satisfied with the appearance of his eyes. This report describes a rare clinical case of conjunctival prolapse and provides a reference for surgeons treating similar complications.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 641-645, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204911

RESUMO

OBJECTIVE: To clone the promoter sequence of acute monocytic leukemia new antigen gene.MLAA-34 and identify its promoter core region. METHODS: The full-length fragment of MLAA-34 gene promoter region was amplified by PCR, then was ligated into pGL3-Basic vector, and the recombinant plasmid was cloned. Constructed a series of MLAA-34 gene promoter 5' flanking region truncated plasmid. These recombinant plasmids were transfected into U937 and HEK293 cells, and the dual luciferase reporter gene was used to detect the promoter activity of each fragment to determine the minimum active region. Transcription factor binding sites were analyzed by bioinformatics methods. RESULTS: The recombinant plasmid containing MLAA-34 promoter sequence and its truncated plasmid were successfully constructed, and the promoter activity was significantly increased as compared with the empty vector (P<0.001). The minimal active region of MLAA-34 located between 402 bp and 200 bp. It contained multiple transcription factor binding sites such as E2F1, MZF-1, SP1, USF2 and STAT3. CONCLUSION: The promoter of luciferase reporter gene has been successfully constructed with different deletion fragments of MLAA-34, and its core promoter region may contain multiple transcription factor sequence.


Assuntos
Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Leucemia Monocítica Aguda , Adulto , Clonagem Molecular , Genes Reporter , Células HEK293 , Humanos , Leucemia Monocítica Aguda/genética , Luciferases , Regiões Promotoras Genéticas
6.
Artigo em Inglês | MEDLINE | ID: mdl-31150065

RESUMO

CONTEXT: LH/hCG receptor (LHR) expression has been shown to be regulated post-transcriptionally by LHR mRNA binding protein (LRBP) in rodent and human ovaries. LRBP was characterized as being mevalonate kinase. The gene that encodes mevalonate kinase is a member of a family of genes that encode enzymes involved in lipid synthesis and are regulated by the transcription factor, sterol regulatory element binding proteins (SREBPs). OBJECTIVE: The present study examined the regulation of LHR mRNA expression in human granulosa-lutein cells in response to alterations in cholesterol metabolism. DESIGN: Using atorvastatin, an inhibitor of HMG CoA reductase to inhibit cholesterol biosynthesis, we examined its effect on LHR mRNA expression. The effect of atorvastatin on SREBP protein and mRNA expression as well as LHR mRNA binding protein expression was examined. Finally, the effect of atorvastatin on hCG -stimulated progesterone production and the expression of key steroidogenic enzymes was also examined. RESULTS: The results showed that statin treatment reduced LHR mRNA expression by increasing the levels of SREBP1a and SREBP2, leading to an increase in LRBP. RNA gel shift assay showed increased binding of LHR mRNA to LRBP occurred in response to atorvastatin leading to LHR mRNA degradation. The granulosa-lutein cells pretreated with atorvastatin also showed decreased responsiveness to hCG by decreasing the mRNA and protein expression of steroidogenic enzymes. Atorvastatin also attenuated LH/hCG-induced progesterone production. CONCLUSION: These results imply that LHR mRNA expression by the human granulosa-lutein cells is regulated by cholesterol, through a mechanism involving SREBP-SCAP serving as the cholesterol sensor.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31195215

RESUMO

Basilepta melanopus is a serious insect pest of tea plantations in southern China. This tea pest poses a great threat to the tea industry in China. No effective and environmentally friendly methods have been established to control this pest at present. Olfactory genes play key roles in insect behaviour, and can potentially be used as targets for developing environmentally-friendly approaches for pest control. In this study, we produced a transcriptome derived from dissected antennae from B. melanopus using high-throughput sequencing. We identified gene families that are potentially involved in odorant reception and detection, including unigenes encoding 63 odorant receptors (ORs), 16 gustatory receptors (GRs), 18 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs), 46 odorant binding proteins (OBPs), and 19 chemosensory proteins (CSPs). Analyses of tissue expression profiles revealed that all 63 OR transcripts, 14 antennal IRs, one SNMP and six OBPs were predominately expressed in antennae. Real-time quantitative PCR assays were also adapted to examine sex-biased expression of selected antenna-predominant genes. Our results provide valuable information for further functional studies of olfactory genes in B. melanopus and potential novel targets for developing new pest control measures.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 222: 117209, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31200268

RESUMO

A new naphthalenediol-based bis(salamo)-type fluorescent probe H4L for Zn2+ and CN- was reported. Probe H4L showed a highly selective fluorescence enhancement toward Zn2+ over other metal ions including Cd2+, and obtained the L-Zn2+complex can only detect CN- in various anions. Their recognition mechanisms were explained by Job plots, fluorescent and UV-vis titrations, and theoretical calculations. The L-Zn2+complex has been synthesized and structurally characterized using Hirshfeld surface analysis, elemental analyses, IR, UV-Vis and fluorescent spectra. Additionally, the relay probe with the wide adaptability of pH range and excellent stability showed highly selectivity for CN- recognition.

10.
Elife ; 82019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31050342

RESUMO

PAX8 is a prototype lineage-survival oncogene in epithelial ovarian cancer. However, neither its underlying pro-tumorigenic mechanisms nor potential therapeutic implications have been adequately elucidated. Here, we identified an ovarian lineage-specific PAX8 regulon using modified cancer outlier profile analysis, in which PAX8-FGF18 axis was responsible for promoting cell migration in an autocrine fashion. An image-based drug screen pinpointed that PAX8 expression was potently inhibited by small-molecules against histone deacetylases (HDACs). Mechanistically, HDAC blockade altered histone H3K27 acetylation occupancies and perturbed the super-enhancer topology associated with PAX8 gene locus, resulting in epigenetic downregulation of PAX8 transcripts and related targets. HDAC antagonists efficaciously suppressed ovarian tumor growth and spreading as single agents, and exerted synergistic effects in combination with standard chemotherapy. These findings provide mechanistic and therapeutic insights for PAX8-addicted ovarian cancer. More generally, our analytic and experimental approach represents an expandible paradigm for identifying and targeting lineage-survival oncogenes in diverse human malignancies.

11.
Oncol Rep ; 42(1): 273-282, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115564

RESUMO

The present study aimed to construct conditionally replicative adenovirus (CRAds) carrying small hairpin (sh)RNA targeting enhancer of zeste homolog 2 (EZH2), in order to study its effect on inhibiting prostate cancer (PCa) cell growth and invasion. Immunohistochemical analyses of EZH2 was performed in tumor tissue samples from PCa and benign prostate hyperplasia (BPH). The human telomerase reverse transcriptase (hTERT) promoter was chosen to transcriptionally control EZH2 gene expression to obtain adenoviral replication (Ad­hTERT­EZH2shRNA) in human PCa cell lines. The inhibitory effect of Ad­hTERT­EZH2shRNA on EZH2 expression was evaluated by reverse transcription­-quantitative polymerase chain reaction and western blot analyses. Cell Counting Kit­8 assays were used to examine the effects of the Ad­hTERT­EZH2shRNA on cell proliferation. Transwell Matrigel invasion assays were used to detected cell invasion. Immunohistochemistry showed that EZH2 staining was stronger in castration­resistant prostate cancer (CRPC) samples, compared with androgen­dependent prostate cancer (ADPC) samples, and was absent in BPH. Furthermore, EZH2 expression knockdown suppressed PCa cell proliferation and invasion. In addition, it was found that Ad­hTERT­EZH2shRNA selectively replicated and significantly reduced the expression of EZH2 in PCa cells lines. The growth ability and invasion of DU145 and PC3 cells in vitro was effectively inhibited by Ad­hTERT­EZH2shRNA. Silencing the expression of EZH2 led to decreased expression of CCND1 and Ki67 and increased expression of E­cadherin, as determined by western blot analysis. Thus, it was shown that CRAds armed with EZH2 shRNA exhibited significant antitumor effects in human PCa cells. Ad­hTERT­EZH2shRNA may be developed as a treatment for hormone­refractory PCa.

12.
Anal Chem ; 91(9): 6371-6377, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30957493

RESUMO

Two-photon fluorescent imaging that utilizes two near-infrared photons as an excitation source affords higher penetration depth of tissue for biomedical research, compared with one-photon fluorescent imaging. However, the high laser power levels of the excitation source may induce photobleaching of two-photon dyes and photodamage to biosamples, which hampers its wide application for in vivo imaging. Inspired by supramolecular chemistry, we have developed a two-photon excited nanoprobe (TPFN) via host-guest interaction with excellent sensitivity, selectivity, biocompatibility, water solubility, and imaging penetration depth. Notably, this supramolecular assembly can significantly amplify the fluorescence intensities of guest molecules (21-fold increase), thereby affording a detection limit of 0.127 µM for sensing H2O2, which is greatly lower than that of free guest molecules (11.98 µM). In particular, ratiometric fluorescent imaging provides more accurate analysis of intracellular H2O2 via the built-in correction of the internal reference. Importantly, TPFN excited by a two-photon laser provides higher penetration depth for visualizing H2O2 in deeper liver tissues, compared with that of one-photon excitation. Thus, TPFN can serve as a powerful nanoplatform for ratiometric imaging of various species via this facile supramolecular self-assembly strategy.

13.
J Agric Food Chem ; 67(18): 5053-5071, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30986058

RESUMO

Mushroom consumption is a global tradition that is still gaining popularity. However, foraging for wild mushrooms and accidental ingestion of toxic mushrooms can result in serious illness and even death. The early diagnosis and treatment of mushroom poisoning are quite difficult, as the symptoms are similar to those caused by common diseases. Chemically, mushroom poisoning is related to very powerful toxins, suggesting that the isolation and identification of toxins have great research value, especially in determining the lethal components of toxic mushrooms. In contrast, most of these toxins have remarkable physiological properties that could promote advances in chemistry, biochemistry, physiology, and pharmacology. Although more than 100 toxins have been elucidated, there are a number of lethal mushrooms that have not been fully investigated. This review provides information on the chemistry (including chemical structures, total synthesis, and biosynthesis) and the toxicology of these toxins, hoping to inspire further research in this area.


Assuntos
Agaricales/química , Micotoxinas/química , Micotoxinas/toxicidade , Bioprospecção , Tratamento Farmacológico , Humanos
14.
Fitoterapia ; 134: 201-209, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30831199

RESUMO

Eleven new cyathane diterpenoids, designated cyafricanins A-K (1-11), were isolated from the culture broth of the baisidiomycete Cyathus africanus (Nidulariaceae, Bird's nest fungi). Their structures were elucidated by comprehensive analysis of their NMR and HRESIMS data. Cyafricanins A (1) was found to possess an unusual 3,4-seco­carbon skeleton. All compounds were evaluated for their neurotrophic activity in PC-12 cells and anti-neuroinflammatory activity in BV2 microglia cells. All of the diterpenoids showed nerve growth factor induced neurite outgrowth-promoting activity at concentration of 20 µM. Among them, cyafricanin B (2) and cyafricanin G (7) exhibited promising neurotrophic activity, and cyafricanin A (1) showed strong inhibitory effects on both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, molecular docking studies revealed that cyafricanin A (1) showed strong interactions with the iNOs protein in the active cavity.


Assuntos
Anti-Inflamatórios/farmacologia , Cyathus/química , Diterpenos/farmacologia , Microglia/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Diterpenos/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Células PC12 , Ratos
15.
Oncogene ; 38(16): 3047-3060, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30617306

RESUMO

Comprehensive molecular characterization of myriad somatic alterations and aberrant gene expressions at personal level is key to precision cancer therapy, yet limited by current short-read sequencing technology, individualized catalog of complete genomic and transcriptomic features is thus far elusive. Here, we integrated second- and third-generation sequencing platforms to generate a multidimensional dataset on a patient affected by metastatic epithelial ovarian cancer. Whole-genome and hybrid transcriptome dissection captured global genetic and transcriptional variants at previously unparalleled resolution. Particularly, single-molecule mRNA sequencing identified a vast array of unannotated transcripts, novel long noncoding RNAs and gene chimeras, permitting accurate determination of transcription start, splice, polyadenylation and fusion sites. Phylogenetic and enrichment inference of isoform-level measurements implicated early functional divergence and cytosolic proteostatic stress in shaping ovarian tumorigenesis. A complementary imaging-based high-throughput drug screen was performed and subsequently validated, which consistently pinpointed proteasome inhibitors as an effective therapeutic regime by inducing protein aggregates in ovarian cancer cells. Therefore, our study suggests that clinical application of the emerging long-read full-length analysis for improving molecular diagnostics is feasible and informative. An in-depth understanding of the tumor transcriptome complexity allowed by leveraging the hybrid sequencing approach lays the basis to reveal novel and valid therapeutic vulnerabilities in advanced ovarian malignancies.


Assuntos
Neoplasias Ovarianas/genética , Transcriptoma/genética , Processamento Alternativo/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica/métodos , Variação Genética/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pessoa de Meia-Idade , Anotação de Sequência Molecular/métodos , Filogenia , Poliadenilação/genética , Isoformas de Proteínas/genética , Transcrição Genética/genética
16.
Chem Commun (Camb) ; 55(12): 1758-1761, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30664144

RESUMO

A bioluminescent probe, BP-HNO, which exhibits a turn-on response to nitroxyl with high sensitivity and selectivity, is reported for the first time in this work. BP-HNO is free from the interference of biological autofluorescence to afford a high signal-to-noise ratio for bioimaging, and was successfully applied to imaging nitroxyl in live cells and mice.


Assuntos
Corantes Fluorescentes/química , Óxidos de Nitrogênio/química , Animais , Linhagem Celular Tumoral , Humanos , Medições Luminescentes , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Imagem Óptica , Transfecção , Transplante Heterólogo
17.
J Colloid Interface Sci ; 538: 620-629, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30554095

RESUMO

Fenton or Fenton-like technique, as one of the advanced oxidation processes, plays a significant role in the removal of non-easily degradable organic pollutants; however, most of such catalysts are fragile with poor structural integrity under large deformation, thereby restricting their wide applications. Herein, soft copper ferrite nanostructures functionalized silica nanofibrous membranes (CuFe2O4@SNM) were fabricated through a novel strategy with the combination of in-situ dopamine polymerization, ion adsorption, and cohesive precipitation method. Benefiting from the high metallic ion adsorption capacity of polydopamine together with the rapid co-precipitation of adsorbed ions on fiber surface in alkaline solution, the membranes possessed homogenously distributed nanostructured CuFe2O4, large specific surface area, and high pore volume, which are a benefit for the improvement of Fenton-like catalytic activity towards organic pollutants decomposition. The resultant soft CuFe2O4@SNM provided favorable catalytic performance towards organic pollutants with a relatively high degradation degree of 96% in 20 min, a fast removal rate of 0.148 min-1, and outstanding recyclability. The successful preparation of such fascinating ceramic nanofibrous membranes would provide a reference for further exploitation of new type Fenton or Fenton-like catalysts with outstanding softness towards wastewater purification.

18.
ACS Appl Mater Interfaces ; 10(51): 44209-44215, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30525383

RESUMO

Novel superhydrophilic inorganic-based N-halamine nanofibrous membranes with high active chlorine contents, outstanding rechargeability, favorable water swelling resistance, and superior mechanical performance were prepared through the combination of electrospinning and sol-gel processing, which could be applied to the dynamic disinfection of bacteria-contaminated water with high disinfection efficiency, large processing flux, and long-term durability. The successful preparation of such silica nanofiber membranous N-halamine antimicrobial with intriguing properties would provide the reference for developing novel antimicrobial nanofibers for multifunctional applications.


Assuntos
Antibacterianos/química , Desinfecção/métodos , Membranas Artificiais , Nanofibras/química , Staphylococcus aureus/crescimento & desenvolvimento , Microbiologia da Água , Água , Nanofibras/ultraestrutura , Staphylococcus aureus/ultraestrutura
19.
J Hematol Oncol ; 11(1): 141, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572922

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(4): 546-550, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30378307

RESUMO

OBJECTIVE: To determine the expression of microRNA-221 (miR-221) in endometrial tissues and its impact on the proliferation of ectopic endometrial stromal cells. METHODS: Endometrial stromal cells were isolated, cultured and identified from normal endometrial tissues (taken from patients without endometriosis) and ectopic endometrial tissues (taken from patients with ovarian endometriosis). The expression of microRNA-221 was detected by stem-loop qRT-PCR. Changes in the expression of miR-221-3p in endometrial stromal cells exposed to estraldiol (10-8 mol/L) for 48 h were detected. The effects of miR-221-3p inhibitor on the expressions of miR-221-3p, phosphatase and tensin homology deleted on chromosome ten (PTEN) and cell proliferations were compared with those of the negative control (NC, 10 nmol/L). RESULTS: The expression of miR-221-3p in ectopic endometrial tissues was 4.2 times higher than that in normal endometrial tissues (P=0.039): 2.66 times higher in ectopic endometrial stromal cells compared with normal endometrial stromal cells (P=0.029). But no differences in the expression of miR-221-5p were found (P>0.05). No differences in the change of miR-221-3p expression after exposure to estrogen for 48h were found between normal and ectopic stromal cells. Inhibition of miR-221-3p function was associated with decreased cell proliferation (P=0.018) and increased expression of PTEN gene (P=0.021). CONCLUSION: The expression of microRNA-221 is upregulated in ectopic endometrial tissues and ectopic endometrial stroma cells. Inhibiting the function of miR-221-3p may result in increased PTEN expression and decreased cell proliferation in endometrial stromal cells.

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