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1.
Environ Sci Technol ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31738527

RESUMO

The aging effects of sodium hydroxide (NaOH) on ion-exchange membranes were systematically studied, including the membrane properties, desalination performance, and fouling behaviors. After aging in NaOH solution, there were minor changes in the cation-exchange membrane (CEM) properties; however, functional groups (i.e., quaternary amines) on the anion-exchange membranes (AEMs) were converted into benzylic alcohol, alkene, and tertiary amines, respectively, by nucleophilic substitution, Hofmann elimination, and ylide formation. These degradations rendered decreased ion-exchange capacity (IEC), increased electrical resistance, lost hydrophilicity, and weakened mechanical strength. Moreover, severe deteriorations of desalination performance were observed due to the little ion-exchange ability of the degraded AEMs. The desalination rates were restored after cultivating the aged AEMs in acid solution, mainly because the tertiary amines transformed from the hydroxide form (OH-form) to the ionic chlorine form (Cl-form). The restored desalination rates indicated that the main degradation products were tertiary amines. In addition, the antifouling performance decreased in the order of aged OH-form > aged Cl-form > original AEMs due to the reduction of foulant-membrane intermolecular interactions after aging in NaOH solution. The results contribute to establishing a more comprehensive understanding of the effects of alkaline cleaning on IEMs and provide new insights into cleaning-process optimization and membrane modification.

2.
Org Lett ; 21(20): 8501-8505, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31591895

RESUMO

Highly enantioselective cascade double allylations of 1-alkyl-3-alkylindolin-2-imine hydrochlorides with (E)-but-2-ene-1,4-diyl dimethyl dicarbonate leading to tetrahydropyrrolo[2,3-b]indoles with an all-carbon quaternary stereocenter have been developed. This transformation was catalyzed by an iridium catalyst together with our developed chiral cyclic phosphoramidite ligand. The method shows some advantages including an operationally simple protocol, fast reaction, and excellent diastereoselectivity and enantioselectivity. Furthermore, reduction of the obtained products with diisobutyl aluminum hydride provided the pyrrolidinoindolines with three chiral centers in high yields with excellent diastereoselectivity and enantioselectivity.

3.
BMC Cancer ; 19(1): 1020, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664937

RESUMO

BACKGROUND: Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. METHODS: We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. RESULTS: Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT > 48 U/L yielded a hazard ratio of 1.53 (95% CI: 1.19-1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. CONCLUSION: Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.

4.
Carcinogenesis ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570939

RESUMO

The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (284X) and whole genome SNP genotyping were performed on a total of 109 samples of ESCC from ten patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor, and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor-descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.

5.
Pathol Res Pract ; 215(11): 152638, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31551175

RESUMO

AIM: Long non-coding RNA (lncRNA) is currently considered to play an important regulatory role in various diseases, including tumors, at present a hot topic in research. As a non-coding transcription product of imprinted gene, LncRNA H19 is expressed as a parent imprinted maternal allele without protein-coding ability. Increasing evidence indicates that LncH19 may be a new tumor marker for early clinical diagnosis and prognosis judgment. In this study, LncH19 expression was investigated by RNA in situ hybridization for further exploring the clinicopathological role of its expression in esophageal squamous cell cancer (ESCC). METHODS: 121 tumor samples and seven cases of adjacent non-tumor tissues from esophageal cancer patients were detected by RNA in situ hybridization (ISH) and the ISH staining was graded with modified Allred scoring. RESULTS: While no LncH19 expression in the tumor adjacent to normal epithelia was disclosed with the technology, significantly higher levels of LncH19 expression were detected in the tumors obtained from the patients who died within one year after surgery, compared to the expression in those tumors from the patients who survived longer than five years after the same treatment regimen (P = 0.001). In addition, LncH19 expression was verified to correlate with a larger tumor size (P = 0.002) and a higher UICC stage (P = 0.001). CONCLUSION: Our LncH19 ISH data verify the involvement of LncH19 in ESCC. Higher levels of LncH19 expression were not only detected in tumors with larger size and in clinical late stage, but also significantly associated with shorter survival, strongly indicating its clinical significance in the malignant progression of ESCC and useful value as a poor prognostic factor for the patients.

6.
Biochem Biophys Res Commun ; 519(3): 497-504, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31530388

RESUMO

Emerging evidence has uncovered the extremely important roles of long noncoding RNAs (lncRNAs) in the progression of malignant tumors which includes numerous processes of gene regulation. LncRNA NR2F1-AS1 has been confirmed to have close correlation with the tumorigenesis of diverse cancers. However, the underlying regulatory function of it on esophageal squamous cell carcinoma (ESCC) progression is poorly known and thus needs more elucidations. In this study, a markedly elevated expression of NR2F1-AS1 was discovered in ESCC cells. Functional assays demonstrated that NR2F1-AS1 deficiency repressed ESCC progression. Molecular mechanism tests verified that knockdown of NR2F1-AS1 could lower the expression of GLI2 (a key protein molecule of Hedgehog signaling pathway) in ESCC. Additionally, NR2F1-AS1 was confirmed to facilitate ESCC progression via activation of Hedgehog signaling pathway. NR2F1-AS1 activated Hedgehog signaling pathway by regulating GLI2 to upregulate NR2F1 expression in ESCC. Besides, NR2F1 was testified to activate NR2F1-AS1 transcription in ESCC. Final rescue assays further demonstrated that NR2F1 upregulation could reverse the NR2F1-AS1 knockdown-mediated function on ESCC progression. Briefly, NR2F1-induced NR2F1-AS1 promotes ESCC progression through activation of Hedgehog signaling pathway.

7.
J Geriatr Psychiatry Neurol ; 32(6): 291-297, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480980

RESUMO

This study was performed to compare the treatment status between older (≥65 years) and younger adults (18-64 years) with severe mental illness (SMI) and explore factors associated with treatment status in rural China. Persons with SMI were identified in one mental health survey in 2015 in 6 townships of Xinjin County, Chengdu, China. Logistic regressions were conducted to explore factors associated with treatment status. Older adults with SMI, especially major depressive disorder, reported significantly lower rates of treatment than younger group. Older age, longer duration of illness, and poor mental status were risk factors for never-treated status in these patients. Never-treated status (46.3%) and poor treatment status in these older patients are serious issues. Different treatment statuses in these patients had various influencing factors. It is crucial to develop culture-specific, community-based mental health services to improve early identification, diagnosis, treatment, and recovery of older adults with SMI in rural China.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31518715

RESUMO

BACKGROUND & AIMS: Chromoendoscopy with iodine staining is used to identify esophageal squamous dysplasia and esophageal squamous cell carcinomas (ESCCs)-absence of staining indicates suspicious regions of dysplasia. However, screening detects precancerous lesions (mild and moderate dysplasia) that do not require immediate treatment; it is a challenge to which lesions are at risk for progression. We investigated the association between absence of iodine staining at chromoendoscopy screening and lesion progression using 6 years of follow-up data from a population-based randomized controlled trial in China. We then constructed and validated a model to calculate risk of progression to severe dysplasia, carcinoma in situ, or ESCC. METHODS: We collected data from 1468 participants (45-69 years old) who were either negative for iodine staining at a baseline chromoendoscopy or found to have mild or moderate dysplasia in histologic analysis of biopsies in the Endoscopic Screening for Esophageal Cancer study in China, from January 2012 through September 2016; 788 of these participants were re-examined by endoscopy after a median interval of 4.2 years (development cohort). We investigated the association between absence of iodine staining and progression of esophageal lesions using Cox prediction models, considering corresponding baseline pathology findings and patient answers to a comprehensive questionnaire. Patients who did not receive a follow-up examination (n = 680) was used as the validation cohort; outcome events in these patients were identified by annual door to door active interviews or linkage with local electronic registry data. The primary outcome was incident esophageal severe dysplasia, carcinoma in situ, or ESCC. RESULTS: In the development cohort, 11 lesions that did not stain with iodine but were classified as not dysplastic in the histology analysis were found to be severe dysplasia, carcinoma in situ, or ESCC at the follow-up evaluation. These lesions accounted for 39.3% of all progressed lesions (n = 28). In the validation cohort, 6 patients with lesions did not stain with iodine but were classified as not dysplastic by histology had a later diagnosis of ESCC, determined from medical records; these patients accounted for 50.0% of all patients with lesion progression (n = 12) until the closing date of this study. We developed a model based on patient age, body mass index, pathology findings, and baseline iodine staining to calculate risk for severe dysplasia, carcinoma in situ, or ESCC. It identified patients for severe dysplasia, carcinoma in situ, or ESCC in the development set with an area under the curve of 0.868 (95% CI, 0.817-0.920) and in the validation set with an area under the curve of 0.850 (95% CI, 0.748-0.952). Almost no cases would be missed if subjects determined to be high or intermediate-high risk subjects by the model were included in surveillance. CONCLUSIONS: Absence of iodine staining at baseline chromoendoscopy identifies esophageal lesions at risk of progression with a high level of sensitivity. A model that combines results of iodine chromoendoscopy with other patient features identifies patients at risk of lesion progression with greater accuracy than histologic analysis of baseline biopsies.

9.
Small ; 15(42): e1902637, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468738

RESUMO

The atomic structure of free-standing graphene comprises flat hexagonal rings with a 2.5 Å period, which is conventionally considered the only atomic period and determines the unique properties of graphene. Here, an unexpected highly ordered orthorhombic structure of graphene is directly observed with a lattice constant of ≈5 Å, spontaneously formed on various substrates. First-principles computations show that this unconventional structure can be attributed to the dipole between the graphene surface and substrates, which produces an interfacial electric field and induces atomic rearrangement on the graphene surface. Further, the formation of the orthorhombic structure can be controlled by an artificially generated interfacial electric field. Importantly, the 5 Å crystal can be manipulated and transformed in a continuous and reversible manner. Notably, the orthorhombic lattice can control the epitaxial self-assembly of amyloids. The findings reveal new insights about the atomic structure of graphene, and open up new avenues to manipulate graphene lattices.

10.
BMC Cancer ; 19(1): 785, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391026

RESUMO

BACKGROUND: The prognostic role of serum alkaline phosphatase (ALP) has been found in several kinds of solid malignant tumor, but has never been extensively discussed in pancreatic cancer, especially through the application of dynamic survival model which incorporates the varying nature of ALP measurements. METHODS: We conducted a retrospective study which successfully collected 551 histopathologically confirmed pancreatic ductal adenocarcinoma (PDAC) patients from a cancer specialized hospital in southwest China. The association between variant ALP which measured during the whole survival period and the overall survival (OS) of PDAC patients was evaluated by using dynamic Anderson-Gill (AG) model. Exhaustive sensitivity analysis was performed by adopting continuous cut-offs of ALP. RESULTS: After adjusted for possible confounding of serum albumin, total bilirubin and leukocyte counts, AG model revealed that, serum ALP during the survival period was nonlinearly associated with the OS of PDAC: for resected patients, compared with those whose ALP results ranged within the first quartile (P75) quartiles were observed 1.14 (95% CI: 0.29-4.56), 3.93 (95% CI: 1.23-12.60), 3.87 (95% CI: 1.32-11.36) folds of death hazard; whereas in un-resected PDAC patients, the hazard ratios (HRs) were 1.15 (95% CI: 0.79-1.68), 1.92 (95% CI: 1.32-2.78), and 1.97 (95% CI: 1.30-2.98), respectively. Sensitivity analysis revealed that, for both resected and un-resected patients, the results of AG model were robust with regard to various cut-offs of ALP, and an increased ALP was in general associated with significantly increased hazard of death. CONCLUSION: Serum ALP during the survival period was significantly associated with the OS of PDAC patients, especially for resected early stage PDAC patients. Future studies with expanded sample size and refined prospective design should be implemented to corroborate our major findings. Besides, the underlying mechanism for this possible hazardous role of ALP should also be investigated.

11.
Nanoscale ; 11(28): 13431-13439, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31281907

RESUMO

Inexpensive and high-efficiency oxygen reduction reaction (ORR) catalysts play a significant role in achieving practical applications of microbial fuel cells (MFCs). Hence, herein, novel nitrogen (N) and trace iron (Fe) co-doped three-dimensional (3D) porous carbon (NFex-C) was synthesized as an excellent ORR catalyst from an interesting salt-induced silk gel, which was beneficial to the spontaneously formation of porosity and boosted the ORR activity. Among the series of NFex-C, NFe0.5-C (1.20% N-ORR/C, 0.07 at% Fe) possessed a higher specific surface area (538.94 m2 g-1) and pore volume (2.158 cm3 g-1). Note that NFe0.5-C exhibited a significantly higher positive initial potential (0.274 V vs. Ag/AgCl) and half-wave potential (0.095 V vs. Ag/AgCl) than other catalysts and commercial Pt/C (20 wt%); this implied that it possessed prominent ORR catalytic activity. In the MFC tests, the output-voltage and maximum power density of NFe0.5-C were enhanced to 517.37 ± 7.87 mV and 605.35 ± 15.39 mW m-2, respectively. Moreover, NFe0.5-C (0.15 $ g-1) exhibits excellent anti-poisoning ability and is thousands of times cheaper than commercial Pt/C (20 wt%, 220.04 $ g-1); therefore, NFe0.5-C should be a prospective catalyst to substitute precious commercial Pt/C in MFCs and even for application in other types of fuel cells.

12.
Org Biomol Chem ; 17(26): 6461-6464, 2019 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-31218327

RESUMO

An efficient iridium-catalyzed intramolecular enantioselective allylation of quinazolin-4(3H)-one derivatives has been developed, and the corresponding products were obtained with high reactivity and high to excellent enantioselectivity with tolerance of some functional groups, in which our developed chiral cyclic phosphoramidite ligands greatly promoted the iridium-catalyzed reactivity and enantioselectivity.

13.
Org Lett ; 21(13): 5335-5340, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31247765

RESUMO

Chiral nitrogen-containing molecules such as chiral amines, azetidines, and 2-substituted tetrahydroquinolines are important privileged scaffolds in medicinal chemistry. In this paper, an efficient and highly enantioselective chiral phosphoric acid catalyzed asymmetric addition of 2-(vinyloxy)ethanol to imines has been developed for the first time, providing the corresponding chiral amines containing dioxolane acetals that can transform into useful chiral N-heterocycles including azetidines and 2-substituted tetrahydroquinolines with excellent optical purity.

14.
Environ Technol ; : 1-10, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31120337

RESUMO

Octylphenol polyethoxylate (OPnEO) is a potential endocrine-disrupting chemical. Biodegradation of OPnEO was investigated using the bacterium Aeromonas sp. TXBc10 isolated from the influent of tannery waste treatment plant in Hunan Province, China. The bacterium was capable of utilizing OPnEO as the sole source of carbon and energy while OPnEO was degraded under aerobic batch culture conditions. Microbial degradation of OPnEO was studied in batch experiments for optimization of environmental factors. The effect of initial OPnEO concentrations on the degradation was investigated between 100 and 1000 mg·L-1 and the results showed that the biodegradation process conformed to the first-order kinetic model. The optimum pH, temperature, salinity and size of inoculum for OPnEO degradation by Aeromonas sp. TXBc10 was found to be 8.0°C, 30°C, 2.5% and 2.0%, respectively. The major metabolites of OPnEO degradation were identified as short-chain octylphenol polyethoxylate without octylphenol by high-performance liquid chromatography - mass spectrometer, which indicated that sequential cleavage of single ethoxylate units to form OPn-1EC might be the transformation mechanism of strain TXBc10. Considering that strain TXBc10 exhibits prominent advantage for biodegradation of OPnEO, it might serve as a promising candidate for in situ remediation of OPnEO and compounds with similar structure in tannery wastewater.

15.
Org Biomol Chem ; 17(20): 4984-4989, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31066430

RESUMO

A novel selective carbon-carbon single bond cleavage has been disclosed through the copper-catalyzed reaction of 1-alkyl-3-alkylindolin-2-imine hydrochlorides with substituted 1-(bromomethyl)-2-iodobenzenes leading to fused N-heterocycles. Mechanistic studies showed that the intrinsic drive of aromatization and the action of the superbase derived from sodium tert-butoxide and dimethylsulfoxide were the key factors leading to the carbon-carbon single bond cleavage. Furthermore, the obtained N-heterocycles are indoloquinoline derivatives with wide biological activities.

16.
Org Lett ; 21(8): 2498-2503, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30942603

RESUMO

Efficient axially chiral cyclic phosphoric acid catalyzed enantioselective sequential additions of 2-aryl-3 H-indol-3-ones, aldehydes, and diethyl 2-aminomalonate have been developed, and a new type of nitrogen-containing heterocyclic compounds, 2,3-dihydro-1 H-imidazo[1,5- a]indol-9(9a H)-one derivatives, were prepared in good yields and excellent ee values with a wide functional group tolerance, in which the reactivity and enantioselectivity of the substrates were enabled by our newly developed axially chiral cyclic phosphoric acid, ( R)-CYC-9-CPA. Furthermore, the corresponding 1 H-imidazo[1,5- a]indol-9(9a H)-ones were constructed through the easy oxidation of 2,3-dihydro-1 H-imidazo[1,5- a]indol-9(9a H)-one derivatives.

17.
Sci Total Environ ; 676: 155-164, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31035084

RESUMO

The species composition of macroinvertebrate communities is sensitive to environmental changes. However, the influence of human activity over seasons on the functional characteristics of macroinvertebrate communities is poorly understood. To elucidate the effects of agriculture-induced environmental changes on stream ecosystems in cold regions, we conducted a comparative study of an agricultural stream and a forest stream in the Changbai Mountains in northeast China in the summer, autumn, and winter of 2016. Our results showed that agriculture had significant effects on the species and functional composition. Although some sensitive species with "Swimmer" and "Shredder" traits disappeared, there was a significant increase in species with resilience and resistance traits such as "Bi- or multivoltine" in the agricultural stream. This result was attributed to the effects of agricultural practices on habitat stability, heterogeneity of habitats, water quality, and material cycling of the stream ecosystems. Furthermore, functional richness and functional divergence decreased in the agricultural stream, reflecting the strong effects of agricultural disturbance on the resource-use efficiency and functional diversification of communities. In particular, community stability also showed significant decrease in the agricultural stream in the summer, implying a stronger disturbance during this season. Generally, the functional traits and biodiversity of both streams had significant seasonal dynamics. The decrease in biodiversity in the winter indicated that low temperature and freezing are additional critical factors affecting the stability of stream ecosystems in cold regions.


Assuntos
Agricultura , Organismos Aquáticos/fisiologia , Monitoramento Ambiental , Invertebrados/fisiologia , Animais , Ásia , Biodiversidade , Clima , Temperatura Baixa , Ecossistema , Rios
18.
Molecules ; 24(6)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889908

RESUMO

Almost all flowers of the tea plant (Camellia sinensis) are white, which has caused few researchers to pay attention to anthocyanin accumulation and color changing in tea flowers. A new purple-leaf cultivar, Baitang purple tea (BTP) was discovered in the Baitang Mountains of Guangdong, whose flowers are naturally pink, and can provide an opportunity to understand anthocyanin metabolic networks and flower color development in tea flowers. In the present study, twelve anthocyanin components were identified in the pink tea flowers, namely cyanidin O-syringic acid, petunidin 3-O-glucoside, pelargonidin 3-O-beta-d-glucoside, which marks the first time these compounds have been found in the tea flowers. The presence of these anthocyanins seem most likely to be the reason for the pink coloration of the flowers. Twenty-one differentially expressed genes (DEGs) involved in anthocyanin pathway were identified using KEGG pathway functional enrichment, and ten of these DEG's screened using venn and KEGG functional enrichment analysis during five subsequent stages of flower development. By comparing DEGs and their expression levels across multiple flower development stages, we found that anthocyanin biosynthesis and accumulation in BTP flowers mainly occurred between the third and fourth stages (BTP3 to BTP4). Particularly, during the period of peak anthocyanin synthesis 17 structural genes were upregulated, and four structural genes were downregulated only. Ultimately, eight critical genes were identified using weighted gene co-expression network analysis (WGCNA), which were found to have direct impact on biosynthesis and accumulation of three flavonoid compounds, namely cyanidin 3-O-glucoside, petunidin 3-O-glucoside and epicatechin gallate. These results provide useful information about the molecular mechanisms of coloration in rare pink tea flower of anthocyanin-rich tea, enriching the gene resource and guiding further research on anthocyanin accumulation in purple tea.


Assuntos
Antocianinas/metabolismo , Camellia sinensis/genética , Camellia sinensis/metabolismo , Flores/metabolismo , Metaboloma/genética , Pigmentação/genética , Análise de Sequência de RNA , Transcriptoma/genética , Vias Biossintéticas/genética , Análise Discriminante , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genes de Plantas , Análise dos Mínimos Quadrados , Anotação de Sequência Molecular , Análise de Componente Principal , Reprodutibilidade dos Testes
19.
Medicine (Baltimore) ; 98(8): e14454, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813145

RESUMO

BACKGROUND: Our previous studies demonstrate that the major histocompatibility complex (MHC) is associated with the progression of esophageal squamous cell carcinoma (ESCC). HLA-DQA1, which belongs to the MHC Class II family, may be a potential biomarker in ESCC progression. However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized. The purpose of this study is to investigate the relationship of HLA-DQA1 expression with the progression and prognosis of ESCC. METHODS: We analyzed the expression profiles of HLA-DQA1 in esophageal cancer (EC) samples in the TCGA database and validated HLA-DQA1 expression by immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction in matched EC and normal tissues, respectively. The correlation between HLA-DQA1 expression and clinicopathologic characteristics of ESCC was further analyzed. RESULT: Immunohistochemical analysis indicated that the expression level of HLA-DQA1 in ESCC tissues was significantly higher than the matched normal tissues (P < .001). HLA-DQA1 mRNA and protein expression were significantly higher in ESCC tissues compared to the matched normal tissues. Patients with family history negative or with tumor sizes >4 cm were associated with higher HLA-DQA1 expression levels. A prognostic significance of HLA-DQA1 was also found by the Log-rank method, in which high expression of HLA-DQA1 was correlated with a shorter overall survival time. The receiver operating characteristic (ROC) curve analysis yielded the area under the ROC curve value of 0.693. Univariate and multivariate analyses also suggest that high expression of HLA-DQA1 is a potential indicator for poor prognosis of ESCC. CONCLUSIONS: Our results demonstrate that HLA-DQA1 plays an important role in ESCC progression and may be a biomarker for ESCC diagnosis and prognosis, as well as a potential target for the treatment of patients with ESCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Cadeias alfa de HLA-DQ/metabolismo , Idoso , Western Blotting , China , Bases de Dados Factuais , Progressão da Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida
20.
Clin Cancer Res ; 25(10): 3035-3045, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30745298

RESUMO

PURPOSE: Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) in esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: In a retrospective study, the prognostic significance of G-NchiRNA was determined in ESCC tissues. The correlation between seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-NchiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS). RESULTS: Exosomal G-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n = 220) and a validation cohort (n = 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation. CONCLUSIONS: SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.

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