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1.
Muscle Nerve ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994466

RESUMO

INTRODUCTION/AIMS: Corticosteroids have been shown to improve muscle strength and delay loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD) and are considered standard of care despite significant side-effects. The objective of this study is to evaluate whether corticosteroid treatment after LOA is beneficial for cardiac or pulmonary functions among boys with DMD. METHODS: We used the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to characterize associations between corticosteroid use and onset of abnormal left ventricular (LV) function or abnormal percent predicted forced vital capacity (ppFVC) among 398 non-ambulatory boys with DMD. Kaplan-Meier curve estimation was used to compare time to onset by corticosteroid use groups; Cox proportional hazards modeling was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals. RESULTS: We found no differences in time to onset of abnormal LV function by corticosteroid use groups. We observed a longer time from LOA to first abnormal ppFVC in boys that were treated with corticosteroid ≥1 y beyond LOA compared with those with no corticosteroid use or those who stopped corticosteroid use within 1 y of LOA. DISCUSSION: Our findings show no association of corticosteroid use beyond LOA with the onset of abnormal LV function, but a significant association with a delay in onset of abnormal ppFVC. Prospective studies of corticosteroid use in boys with DMD who have lost ambulation may identify benefits and can better elucidate risks, allowing for more effective counseling of patients on continuing treatment after LOA.

2.
Br J Radiol ; 95(1130): 20210918, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34908477

RESUMO

OBJECTIVE: The present study explored the value of preoperative CT radiomics in predicting lymphovascular invasion (LVI) in esophageal squamous cell carcinoma (ESCC). METHODS: A retrospective analysis of 294 pathologically confirmed ESCC patients undergoing surgical resection and their preoperative chest-enhanced CT arterial images were used to delineate the target area of the lesion. All patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Radiomics features were extracted from single-slice, three-slice, and full-volume regions of interest (ROIs). The least absolute shrinkage and selection operator (LASSO) regression method was applied to select valuable radiomics features. Radiomics models were constructed using logistic regression method and were validated using leave group out cross-validation (LGOCV) method. The performance of the three models was evaluated using the receiver characteristic curve (ROC) and decision curve analysis (DCA). RESULTS: A total of 1218 radiomics features were separately extracted from single-slice ROIs, three-slice ROIs, and full-volume ROIs, and 16, 13 and 18 features, respectively, were retained after optimization and screening to construct a radiomics prediction model. The results showed that the AUC of the full-volume model was higher than that of the single-slice and three-slice models. According to LGOCV, the full-volume model showed the highest mean AUC for the training cohort and the validation cohort. CONCLUSION: The full-volume radiomics model has the best predictive performance and thus can be used as an auxiliary method for clinical treatment decision making. ADVANCES IN KNOWLEDGE: LVI is considered to be an important initial step for tumor dissemination. CT radiomics features correlate with LVI in ESCC and can be used as potential biomarkers for predicting LVI in ESCC.

3.
World J Gastrointest Oncol ; 13(11): 1781-1790, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34853650

RESUMO

BACKGROUND: Albumin-bound paclitaxel (ABP) has been used as second- and higher-line treatments for advanced esophageal cancer, and its efficacy and safety have been well demonstrated. Lobaplatin (LBP) is a third-generation platinum antitumor agent; compared with the first two generations of platinum agents, it has lower toxicity and has been approved for the treatment of breast cancer, small cell lung cancer, and chronic granulocytic leukemia. However, its role in the treatment of esophageal cancer warrants further investigations. AIM: To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy (RCT) for locally advanced esophageal cancer. METHODS: Patients with pathologically confirmed advanced esophageal squamous cell carcinoma (ESCC) at our hospital were enrolled in this study. All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT: ABP 250 mg/m2, ivgtt, 30 min, d1, every 3 wk; and LBP, 30 mg/m2, ivgtt, 2 h, d1, every 3 wk. A total of four cycles were scheduled. The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions, 1.8-2.0 Gy/fraction, and 5 fractions/wk. RESULTS: A total of 29 patients were included, and 26 of them completed the treatment protocol. After the induction chemotherapy, the objective response rate (ORR) was 61.54%, the disease control rate (DCR) was 88.46%, and the progressive disease (PD) rate was 11.54%; after the concurrent RCT, the ORR was 76.92%, the DCR was 88.46%, and the PD rate was 11.54%. The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo. Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone (P = 0.0024). Non-hematologic toxicities were tolerable, and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis (13.79%). The main hematologic toxicity was neutropenia, and no grade 4 adverse event occurred. CONCLUSION: Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC, with mild adverse effects. Thus, this protocol is worthy of clinical promotion and application.

4.
Adv Mater ; : e2108178, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34902189

RESUMO

The ability to regulate charge separation is pivotal for obtaining high efficiency of any photoelectrode used for solar fuel production. Vacancy engineering for metal oxide semiconductor photoelectrode is a major strategy but has faced a formidable challenge in bulk charge transport because of the elusive charge self-trapping site. In this work, a new deep eutectic solvent to engineer bismuth vacancies (Bivac ) of BiVO4 photoanode is reported; the novel Bivac can remarkably increase the charge diffusion coefficient by 5.8 times (from 1.82 × 10-7 to 1.06 × 10-6 cm2 s-1 ), which boosts the charge transport efficiency. Through further loading CoBi cocatalyst to enhance charge transfer efficiency, the photocurrent density of BiVO4 photoanode with optimal Bivac concentration reaches 4.5 mA cm-2 at 1.23 V vs reversible hydrogen electrode under AM 1.5 G illumination, which is higher than that of previously reported Ovac engineered BiVO4 photoanode where the BiVO4 photoanode is synthesized by a similar procedure. This work perfects a cation defect engineering that enables the potential capability to equate the charge transport properties in different types of semiconductor materials for solar fuel conversion.

5.
Adv Sci (Weinh) ; : e2103838, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923767

RESUMO

Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady-state hematopoiesis in young mice. Hemgn-/- HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn-/- HSPCs are enriched for gene sets related to interferon gamma (IFN-γ) signaling. Hemgn-/- HSPCs show enhanced responses to IFN-γ treatment and increased aging over time. Blocking IFN-γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn-/- HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T-cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN-γ-treated Hemgn-/- mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN-γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34758183

RESUMO

Small-molecule binding assays to target proteins are a core component of drug discovery and development. While a number of assay formats are available, significant drawbacks still remain in cost, sensitivity, and throughput. To improve assays by capitalizing on the power of DNA sequence analysis, we have developed an assay method that combines DNA encoding with split-and-pool sample handling. The approach involves affinity labeling of DNA-linked ligands to a protein target. Critically, the labeling event assesses ligand binding and enables subsequent pooling of several samples. Application of a purifying selection on the pool for protein-labeled DNAs allows detection of ligand binding by quantification of DNA barcodes. We demonstrate the approach in both ligand displacement and direct binding formats and demonstrate its utility in determination of relative ligand affinity, profiling ligand specificity, and high-throughput small-molecule screening.

7.
Theranostics ; 11(20): 10012-10029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815801

RESUMO

Various living organisms have proven to influence human health significantly, either in a commensal or pathogenic manner. Harnessing the creatures may remarkably improve human healthcare and cure the intractable illness that is challenged using traditional drugs or surgical approaches. However, issues including limited biocompatibility, poor biosafety, inconvenience for personal handling, and low patient compliance greatly hinder the biomedical and clinical applications of living organisms when adopting them for disease treatment. Microneedle arrays (MNAs), emerging as a promising candidate of biomedical devices with the functional diversity and minimal invasion, have exhibited great potential in the treatment of a broad spectrum of diseases, which is expected to improve organism-based therapies. In this review, we systemically summarize the technologies employed for the integration of MNAs with specific living organisms including diverse viruses, bacteria, mammal cells and so on. Moreover, their applications such as vaccination, anti-infection, tumor therapy and tissue repairing are well illustrated. Challenges faced by current strategies, and the perspectives of integrating more living organisms, adopting smarter materials, and developing more advanced technologies in MNAs for future personalized and point-of-care medicine, are also discussed. It is believed that the combination of living organisms with functional MNAs would hold great promise in the near future due to the advantages of both biological and artificial species.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34769735

RESUMO

Despite making significant progress in tackling its HIV epidemic, South Africa, with 7.7 million people living with HIV, still has the biggest HIV epidemic in the world. The Government, in collaboration with developmental partners and agencies, has been strengthening its responses to the HIV epidemic to better target the delivery of HIV care, treatment strategies and prevention services. Population-based household HIV surveys have, over time, contributed to the country's efforts in monitoring and understanding the magnitude and heterogeneity of the HIV epidemic. Local-level monitoring of progress made against HIV and AIDS is increasingly needed for decision making. Previous studies have provided evidence of substantial subnational variation in the HIV epidemic. Using HIV prevalence data from the 2016 South African Demographic and Health Survey, we compare three spatial smoothing models, namely, the intrinsically conditionally autoregressive normal, Laplace and skew-t (ICAR-normal, ICAR-Laplace and ICAR-skew-t) in the estimation of the HIV prevalence across 52 districts in South Africa. The parameters of the resulting models are estimated using Bayesian approaches. The skewness parameter for the ICAR-skew-t model was not statistically significant, suggesting the absence of skewness in the HIV prevalence data. Based on the deviance information criterion (DIC) model selection, the ICAR-normal and ICAR-Laplace had DIC values of 291.3 and 315, respectively, which were lower than that of the ICAR-skewed t (348.1). However, based on the model adequacy criterion using the conditional predictive ordinates (CPO), the ICAR-skew-t distribution had the lowest CPO value. Thus, the ICAR-skew-t was the best spatial smoothing model for the estimation of HIV prevalence in our study.


Assuntos
Epidemias , Infecções por HIV , Teorema de Bayes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Prevalência , África do Sul/epidemiologia
9.
J Nematol ; 532021.
Artigo em Inglês | MEDLINE | ID: mdl-34761225

RESUMO

A stunt nematode species, Quinisulcius curvus, recovered from the rhizosphere of sea randa (Guettarda speciosa), is described and characterized herein based on integrative taxonomy. Morphometrics and distribution of all reported populations of Q. curvus are also discussed. The Chinese population of Q. curvus displayed slight variation in stylet length; however, the rest of the characters matches well with the original description. This is the first record of Q. curvus from Hainan, China, and the first molecular characterization for this species. Phylogenetic analysis based on partial 18S, 28S and ITS sequences placed Q. curvus with related stunt nematodes species, but clearly separated from them. The present study expanded the geographic record and provided molecular data on Q. curvus from China.

10.
ACS Appl Mater Interfaces ; 13(46): 55102-55111, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34762409

RESUMO

Although research progress on mimicking natural photosynthesis for solar-to-fuel conversion has been continuously made, exploring broadband spectral-responsive materials with suitable band positions and high stability still remains a huge challenge. Herein, we, for the first time, report novel AsP nanosheets (NSs) with P-type semiconducting property and enough negative conduction band, which can work as a stable near-infrared (NIR) region-responsive electron donor for water reductive hydrogen (H2) production. To mimic photosystem I, Au nanorods (NRs) act as electron transport media, which are also responsible for the enhanced electric field nearby, and 1T-MoS2 NSs as a hydrogen evolution catalyst are orderly coupled with AsP NSs with a sheet-rod-sheet structure by electrostatic self-assembly. The cascaded band level alignment enables unidirectional electron flow from AsP to Au and then to MoS2, and the optimum H2 production rate of the MoS2-Au-AsP ternary heterojunction reaches 125.52 µmol g-1 h-1 with good stability even after being stored for several months under light irradiation with a wavelength longer than 700 nm. This work provides a platform that is energetically tailored to drive a solar broad-spectrum fuel generation, including CO2 reduction and N2 fixation.

11.
Mitochondrial DNA B Resour ; 6(10): 3041-3043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595335

RESUMO

The mountain dragon, Diploderma vela, is an endemic and protected valley lizard that inhabits the upper Lantsang Valley in West China. In this study, we sequenced the complete mitochondrial genome of a male individuals of D. vela using next-generation sequencing methodologies. The complete mitogenome is 16,432 bp in length and contains one noncoding control regions, 13 protein-coding, 22 transfer RNA and two ribosomal RNA genes. The mitogenome content and structure of D. vela was consistent with the previously published representatives of the family. A Bayesian phylogenetic analysis using the complete mitochondrial genomes of Agamidae fully resolved D. vela in the Draconinae, a result consistent with previous investigations. This study provides bioinformatic data for better understanding the evolution and the phylogenetic history of the mountain dragon.

12.
J Manag Care Spec Pharm ; 27(8): 1142-1152, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34337992

RESUMO

BACKGROUND: Before 2007, erythropoiesis-stimulating agents (ESAs) were the highest-expenditure drug in the Medicare system. In 2007, CMS issued a reimbursement policy change for ESAs used by cancer patients. However, empirical evidence is currently lacking to evaluate medical costs after the policy change, especially by sex and racial/ethnic groups. OBJECTIVE: To examine the impact of the Medicare reimbursement policy change and associated racial/ethnic and sex disparities on medical costs for cancer patients who were new users of ESAs. METHODS: This study was an exploratory retrospective treatment effectiveness study, which used SEER-Medicare linked data. A difference-in-difference design was used that incorporated a control group of patients with chronic kidney disease. A generalized linear model, with a log link and a gamma distribution, was used to examine medical costs. RESULTS: The Medicare reimbursement policy change was statistically significantly associated with an 11% (95% CI = 2%-20%) reduction in anemia-related costs, including a 10% (95% CI = 1%-19%) reduction in Medicare payment and an 18% (95% CI = 10%-26%) reduction in patient cost sharing. For total medical costs, the policy change was statistically significantly associated with a 12% (95% CI = 6%-18%) reduction, including an 11% (95% CI = 5%-18%) reduction in Medicare payment and a 14% (95% CI = 7%-20%) reduction in patient cost sharing. Medical costs were reduced in patients who were male and those who were White but remained the same for patients who were female and those who were Black, Hispanic, and other races or ethnicities. CONCLUSIONS: Anemia-related and total medical costs associated with ESAs used by cancer patients with chemotherapy-induced anemia were reduced after the Medicare reimbursement policy change. However, the policy change was only effective for patients who were male and those who were White. The policy change had no effect on patients who were female and those of racial/ethnic minorities. DISCLOSURES: This study was funded by the SPARC Research Grant. The funder had no role in any part of this study. This study used the linked SEER-Medicare database. The interpretation and reporting of the data are the sole responsibility of the authors. The authors have nothing to disclose.


Assuntos
Anemia/tratamento farmacológico , Custos de Cuidados de Saúde , Disparidades em Assistência à Saúde/etnologia , Hematínicos/economia , Medicare , Políticas , Mecanismo de Reembolso , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematínicos/uso terapêutico , Humanos , Falência Renal Crônica , Masculino , Estudos Retrospectivos , Programa de SEER , Estados Unidos
13.
Mitochondrial DNA B Resour ; 6(9): 2494-2495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377803

RESUMO

The complete mitogenome of Ips calligraphus was sequenced, the length was 19,144 bp which consists of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a major non-coding AT-rich region (GenBank accession no. MW589547). All of 13 protein-coding genes (PCGs) started with ATN. 12 PCGs used the typical stop codon 'TAA,' while ATP8 terminated with stop codon 'TAG.' Phylogenetic analyses were performed using mitochondrial PCGs for the I. calligraphus and other 18 species within the Scolytinae. The I. calligraphus was clustered together with the other two Ips species in tribe Ipini which were closely related to Xyleborini and Dryocoetini.

14.
Endocr J ; 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34456194

RESUMO

Chronic stress affects the reproductive health of mammals; however, the impact of adrenocorticotropin hormone (ACTH) level elevation during chronic stress on the reproduction of weaned sows remains unclear. In this study, nine weaned sows with the same parturition date were randomly divided into control group (n = 4) and ACTH group (n = 5). Each group received intravenous administration of ACTH three times daily for 7 days. Blood samples were collected every 3 h after injection. A radioimmunoassay was used to measure the concentrations of cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4) and estradiol-17ß (E2) in the blood. Estrus was determined according to changes in the vulva and the boar contact test. The mRNA expressions of glucocorticoid receptor, FSH receptor, LH receptor (LHR) in the corpus luteum (CL) were detected by qRT-PCR. The results showed that ACTH administration substantially delayed the initiation of estrus and the pre-ovulatory LH peak. The sows of control group ovulated within 10 days and the ovulation rate was 100%, while it was 60% in the ACTH group. Two sows of ACTH group showed pseudo-estrus. The E2 concentrations significantly decreased in the ACTH group at 36 h, 42 h and 66 h of the experimental period. The P4 concentrations in the ACTH group significantly decreased at 132, 138, and 147 h of the experimental period. ACTH significantly reduced the LHR mRNA expression in CLs. In conclusion, long-term repeated ACTH administration affects the endocrinology, estrus onset, and ovarian function of weaned sows.

15.
Mitochondrial DNA B Resour ; 6(9): 2652-2653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34435108

RESUMO

Octodonta nipae (Maulik 1921) is a dangerous forestry quarantine pest, which mainly harms palms. In the present study, we determined complete mitogenome of O. nipae. This mitogenome was 15,397 bp in length (GenBank Accession no. MW802252), which contained 2 ribosomal RNA genes, 22 transfer RNAs, 13 protein-coding genes (PCGs) and one non-coding AT-rich region with the length of 883 bp. All of the 22 tRNA genes displayed a typical clover-leaf structure, with the exception of tRNAPhe, tRNALeu, tRNAAsn, tRNAPro and tRNAThr. Twelve PCGs were initiated by ATN codons, and NAD1 started with TTG. Ten PCGs used the typical stop codon 'TAA' and 'TGA', while three PCGs (COX2, COX3, NAD4) used the incomplete stop codons 'TA' or 'T'. Phylogenetic tree demonstrated that O. nipae belongs to the family Chrysomelidae and closer to the superfamily Cassidinae.

16.
Mitochondrial DNA B Resour ; 6(9): 2683-2685, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34435118

RESUMO

The mitochondrial genome has been widely used in the study of phylogeny and species-level evolution. Here, we sequenced and analyzed the full mitogenome of Tetrastichus howardi, an important natural enemy of many lepidopteran pests. The complete mitochondrial genome has 14,791 nucleotides, containing 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and a partial control region. All the 13 PCGs started with typical ATN (ATA, ATG, and ATT) codon. Among 13 PCGs, nine genes terminated with the stop codon TAA and four genes terminated with T. Our study provides information on comparative mitogenomics of Eulophidae.

17.
Cell Death Discov ; 7(1): 224, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34455417

RESUMO

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

18.
Mitochondrial DNA B Resour ; 6(8): 2302-2304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34291165

RESUMO

Trichogramma chilonis Ishii is an important natural enemy of several lepidopterous pests on crops. In this study, we sequenced the complete mitochondrial genome of T. chilonis (GenBank accession number MW789210). The length of the complete mitochondrial genome was 16,147 bp, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a non-coding control region. The overall base composition of the genome in descending order was 44.8% T, 41.8% A, 9.0% G and 4.5% C, with a significant AT bias of 86.6%. Phylogenetic analysis indicated that T. chilonis had a close relationship with Trichogramma ostriniae.

19.
Virchows Arch ; 479(5): 905-917, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34313839

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in East Asia. Surgical resection is currently the typical treatment. However, due to the highly invasive and metastatic characteristic of the disease, the mortality rate is still high. A search for potential prognostic biomarkers and therapeutic targets is very necessary. Here, we studied the expression of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine protein kinase, in ESCC and its influence on prognosis. A total of 112 cases of ESCC and paired adjacent normal tissues (NT) were organized in tissue microarray (TMA) from the Nantong First People's Hospital. Our analysis of TMA revealed that Pyk2 levels were higher in ESCC than in paired adjacent NT by immunohistochemistry (p<0.001). Western blot and real-time quantitative PCR analysis (p=0.0359) also reached similar conclusions. To further explore the significance of Pyk2 in ESCC, another set of tissue microarrays was collected from the Affiliated Hospital of Nantong University, which includes 241 consecutive patients undergoing radical surgery for ESCC, to perform IHC scores. We demonstrated that the expression level of Pyk2 was positively correlated with N stage (node negative versus node positive, p=0.02) and clinical stage (I + II versus III + IV, p=0.042). Univariate and multivariate analyses suggested that high Pyk2 expression was an independent prognostic factor for overall survival with ESCC. Cell function studies found that Pyk2 promoted tumor proliferation and migration and reduced apoptosis. Pyk2 knockdown enhanced the sensitivity to cisplatin in ESCC cells. Western blot analysis confirmed that Pyk2 may promote tumor progression by activating the Akt signaling pathway.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Quinase 2 de Adesão Focal/metabolismo , Idoso , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/enzimologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Resultado do Tratamento
20.
World J Gastroenterol ; 27(19): 2366-2375, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34040328

RESUMO

BACKGROUND: Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators. AIM: To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance. METHODS: EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B9, B12, B1, C, B2 and B6), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed. RESULTS: In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B2 deficiency and weight loss were found in these patients, and the proportions of vitamin B2 and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B2 and B6 and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002). CONCLUSION: Vitamin A, D, C and B2 were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.


Assuntos
Neoplasias Esofágicas , Vitaminas , Ácido Ascórbico , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Humanos , Masculino , Estado Nutricional , Vitamina A
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