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1.
Cell Cycle ; : 1-16, 2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-33966609

RESUMO

Mismatch repair (MMR) plays an important role in the occurrence and development of tumors. At present, it is widely believed that MMR is a protective mechanism of tumors that plays a critical role in the progresses of cancer. In this study, 34 genes related to MMR selected from Gene Ontology (GO) database were scored by single sample Gene sets enrichment analysis (ssGSEA), and eight cancers were screened from 23 TCGA solid cancers to investigate the clinical significance of MMR score. MMR had different effects on the prognosis of the eight tumors, with a protective effect in three cancers and functioning as a risk factor in the remaining five cancers. We used unsupervised clustering to divide the patients into four clusters. We found that the immune and metabolic status of the four clusters were extremely different, among which cluster1 had the lowest tumor purity and the most complex microenvironment; this may explain its poor prognosis and immunotherapy effect. In summary, MMR scores can improve the predictive ability and provide effective guidance for immunotherapy in individual type of tumors.

3.
Proc Natl Acad Sci U S A ; 118(16)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33846242

RESUMO

Precision medicine in oncology leverages clinical observations of exceptional response. Toward an understanding of the molecular features that define this response, we applied an integrated, multiplatform analysis of RNA profiles derived from clinically annotated glioblastoma samples. This analysis suggested that specimens from exceptional responders are characterized by decreased accumulation of microglia/macrophages in the glioblastoma microenvironment. Glioblastoma-associated microglia/macrophages secreted interleukin 11 (IL11) to activate STAT3-MYC signaling in glioblastoma cells. This signaling induced stem cell states that confer enhanced tumorigenicity and resistance to the standard-of-care chemotherapy, temozolomide (TMZ). Targeting a myeloid cell restricted an isoform of phosphoinositide-3-kinase, phosphoinositide-3-kinase gamma isoform (PI3Kγ), by pharmacologic inhibition or genetic inactivation disrupted this signaling axis by reducing microglia/macrophage-associated IL11 secretion in the tumor microenvironment. Mirroring the clinical outcomes of exceptional responders, PI3Kγ inhibition synergistically enhanced the anti-neoplastic effects of TMZ in orthotopic murine glioblastoma models. Moreover, inhibition or genetic inactivation of PI3Kγ in murine glioblastoma models recapitulated expression profiles observed in clinical specimens isolated from exceptional responders. Our results suggest key contributions from tumor-associated microglia/macrophages in exceptional responses and highlight the translational potential for PI3Kγ inhibition as a glioblastoma therapy.

4.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(3): 257-262, 2021 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33927072

RESUMO

OBJECTIVES: To investigate the clinical characteristics of patients with listeriosis and to provide a basis for diagnosis, treatment, prevention and control of hospital infection. METHODS: A total of 10 inpatients, who suffered from the listeriosis in Xiangya Hospital, Central South University from January 2013 to June 2019, were retrospectively collected for this study. The characteristics of the patients' age, gander, basic information, case type, clinical manifestations, first consultation department, days of diagnosis, infection indicator, specimen type, results of drug sensitivity, treatment plan, hospital infection or not, outcome, follow-up data were analyzed. RESULTS: Two cases were pregnant women and other were non-pregnant adults among 10 patients with listeriosis. Among them, there were 3 cases with hospital acquired infection. The age of patient onset was 27-71 years old, and the time from onset to diagnosis was 5-36 days. Five cases had fever, and other 5 cases had not fever. There were headache, fatigue, local pain, and other specialized symptoms in the 10 patients.The white blood cell count,the neutrophil ratio, the inflammatory index C-reactive protein, the procalcitonin were all increased, and the erythrocyte sedimentation was accelerated in the 10 patients.All the patients were sensitive to ampicillin, penicillin G, meropenem, and compound sinomine. CONCLUSIONS: Listeriosis often affects the patients with low immunity, which often leads to misdiagnosis or missed diagnosis in clinic.So early prevention, early diagnosis, and early treatment can reduce mortality; it is important for departments of nosocomial infection management to manage patients' diet for avoiding outbreaks of listeriosis in hospital.


Assuntos
Listeria monocytogenes , Listeriose , Complicações Infecciosas na Gravidez , Adulto , Idoso , Feminino , Humanos , Listeriose/diagnóstico , Listeriose/tratamento farmacológico , Listeriose/epidemiologia , Meropeném , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos
5.
J Cell Mol Med ; 25(8): 3870-3884, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33611848

RESUMO

Endoplasmic reticulum (ER) stress has considerable impact on cell growth, proliferation, metastasis, invasion, angiogenesis and chemoradiotherapy resistance in various cancers. However, the effect of ER stress on the outcomes of glioma patients remains unclear. In this study, we established an ER stress risk model based on The Cancer Genome Atlas (TCGA) glioma data set to reflect immune characteristics and predict the prognosis of glioma patients. Survival analysis indicated that there were significant differences in the overall survival (OS) of glioma patients with different ER stress-related risk scores. Moreover, the ER stress-related risk signature, which was markedly associated with the clinicopathological properties of glioma patients, could serve as an independent prognostic indicator. Functional enrichment analysis revealed that the risk model correlated with immune and inflammation responses, as well as biosynthesis and degradation. In addition, the ER stress-related risk model indicated an immunosuppressive microenvironment. In conclusion, we present an ER stress risk model that is an independent prognostic factor and indicates the general immune characteristics in the glioma microenvironment.

6.
Medicine (Baltimore) ; 100(5): e24503, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592903

RESUMO

ABSTRACT: Recently, the coronavirus disease 2019 (COVID-19) epidemic has greatly threatened global public health. The responsibility of healthcare-associated infection control professionals (ICPs) is to prevent and control the nosocomial infections. The mental health status of ICPs deserves more attention, however, the correlational research is still lacking. This study aims to investigate the incidence and risk factors of mental health status among ICPs in China during the outbreak of COVID-19.A national cross-sectional survey was performed. The online questionnaire was completed by 9228 ICPs from 3776 hospitals throughout China. Data collection tools were used, including demographics data questionnaire, the Chinese version of the 12-item general health questionnaire (GHQ-12) and the Chinese version of the psychological capital questionnaire (PCQ) for medical staff. Univariate and multivariable analyses were conducted.The total score of mental health of Chinese ICPs was 3.45 ±â€Š2.57. 5608 (60.77%) ICPs might have mental health problems. The psychological capital was in the upper-middle level with an average score of 3.72 ±â€Š0.38. An increased mental health problem risk was associated with the greater self-efficacy and working in the public hospital; a significantly lower risk was obtained by working in the second-class hospital rather than in the third-class hospitals. Besides, mental health problem risk of ICPs working in hospitals of the western economic region or northeast economic region was more significant than that in hospitals of the central economic region. However, a lower risk was caused by the unmarried than married, and working years in department ≤1 year contributed to the lower risk than that >20 years. Moreover, fewer working hours per week, higher values of hope, and optimism each were contributed to a lower risk.Chinese healthcare-associated ICPs were under different levels of mental health problems in fighting against COVID-19. More importantly, we should actively deal with the mental health problem of ICPs and help them get rid of psychological disorders.


Assuntos
Infecção Hospitalar , Profissionais Controladores de Infecções , Controle de Infecções , Exposição Ocupacional , Estresse Ocupacional , Adulto , /prevenção & controle , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Estudos Transversais , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Profissionais Controladores de Infecções/psicologia , Profissionais Controladores de Infecções/estatística & dados numéricos , Masculino , Saúde Mental/estatística & dados numéricos , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/estatística & dados numéricos , Estresse Ocupacional/epidemiologia , Estresse Ocupacional/etiologia , Estresse Ocupacional/prevenção & controle , Medição de Risco , Inquéritos e Questionários
7.
Clin Infect Dis ; 71(Suppl 4): S372-S378, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367579

RESUMO

More than 3 decades have passed since infection control was implemented nationwide in China in 1986. A comprehensive set of regulations and guidelines has been developed, and almost all hospitals have established infection control teams. However, compliance is variable and is usually suboptimal. The incidence of certain multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP), is increasing, and associated infections are mainly hospital-acquired in China. Carbapenem-resistant Pseudomonas aeruginosa has remained relatively stable, whereas methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterobacter faecium have been decreasing. The spread of CRAB and CRKP in China is largely mediated by dominant high-risk lineages, namely, clonal complex 92 for CRAB and sequence type 11 for CRKP. However, challenges owing to MDROs bring opportunities for rethinking, taking coordinated action, building capacity, changing behavior, and performing studies that reflect everyday situations in the Chinese healthcare system.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Farmacorresistência Bacteriana , Humanos , Controle de Infecções , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana
8.
Clin Infect Dis ; 71(Suppl 4): S427-S435, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367580

RESUMO

BACKGROUND: Considering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018. METHODS: In total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines. RESULTS: In 2015-2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae. CONCLUSIONS: Given their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.


Assuntos
Infecções Intra-Abdominais , Infecções Urinárias , Antibacterianos/farmacologia , Compostos Azabicíclicos , China/epidemiologia , Farmacorresistência Bacteriana , Enterobacteriaceae , Humanos , Imipenem , Infecções Intra-Abdominais/epidemiologia , Testes de Sensibilidade Microbiana , Sistema Respiratório , Estados Unidos , Infecções Urinárias/epidemiologia
9.
Clin Infect Dis ; 71(Suppl 4): S337-S362, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367581

RESUMO

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.


Assuntos
Fístula , Infecções Intra-Abdominais , Cirurgiões , China , Cuidados Críticos , Humanos , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/tratamento farmacológico
10.
Biofabrication ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33348331

RESUMO

T-cell immunotherapy holds promise for the treatment of cancer, infection, and autoimmune diseases. Nevertheless, T-cell therapy is limited by low cell expansion efficiency ex vivo and functional deficits. Here we describe two 3D bioprinting systems made by different biomaterials that mimic the in vivo formation of natural lymph vessels and lymph nodes which modulate T-cell with distinct fates and functions. We observe that coaxial alginate fibers promote T-cell expansion, less exhausted and enable CD4+ T-cell differentiation into central memory-like phenotype (Tcm), CD8+ T-cells differentiation into effector memory subsets (Tem), while alginate-gelatin scaffolds bring T-cells into a relatively resting state. Both of the two bioprinting methods are strikingly different from a standard suspension system. The former bioprinting method yields a new system for T-cell therapy and the latter method can be useful for making an immune-chip to elucidate links between immune response and disease.

11.
J Clin Neurosci ; 82(Pt A): 166-172, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33317727

RESUMO

BACKGROUND: Over the past decade, the endoscopic transnasal transsphenoidal approach for pituitary adenomas has been widely adopted among neurosurgeons. However, olfactory disturbances have been observed after this procedure, and few studies on long-term (>6 mo) olfactory disturbance after endoscopic transnasal transsphenoidal pituitary adenoma surgery have been conducted. Although we perform minimally invasive endoscopic surgery, some patients continue to experience hyposmia, with some even experience long-term hyposmia. This impairment results in a considerable loss in quality of life. We present a series of patients who underwent minimally invasive single-nostril TSS for pituitary adenoma, including evaluation of their olfactory function. We further investigated the related risk factors for long-term olfactory dysfunction. METHODS: One hundred sixty-one consecutive patients who met the study criteria underwent the single-nostril endoscopic transsphenoidal approach by the senior author. The Smell Diskettes Olfaction Test was used to evaluate olfactory function. RESULTS: Postoperative olfactory disturbance in patients treated with endoscopic transnasal TSS is frequent. Of the study population, 67.1% of the patients were hyposmic or anosmic and 14.9% had long-term olfactory dysfunction. We also performed multivariate logistic regression analysis to compare the characteristics of patients with long-term olfactory dysfunction. Nasal symptoms (odds ratio [OR], 6.77) and smoking (OR, 14.77) were associated with long-term olfactory dysfunction after transnasal TSS. CONCLUSIONS: Significant disturbances in olfactory performance occur after single-nostril transnasal TSS for pituitary adenoma. Furthermore, preoperative nasal disease and smoking appear to be risk factors for long-term olfactory dysfunction. Physicians should address clinical findings related to olfactory function and provide appropriate care.


Assuntos
Adenoma/cirurgia , Endoscopia/efeitos adversos , Transtornos do Olfato/etiologia , Neoplasias Hipofisárias/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Qualidade de Vida , Olfato , Resultado do Tratamento
12.
Front Neurol ; 11: 540911, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250840

RESUMO

Objectives: This article aims to evaluate the safety and effectiveness of endoscope-assisted surgery for chronic subdural hematoma (cSDH) in comparison with the burr-hole craniostomy. Methods: An electronic literature research was performed in MEDLINE, the Cochrane library, and EMBASE from the inception to February 18, 2020. A systematic review with meta-analyses was conducted to compare the efficacy of endoscope-assisted surgery with Burr-hole Craniostomy (BHC) surgery. Results: This meta-analysis included four studies comprising 441 patients. Endoscope-assisted surgery significantly decreased the risk of recurrence in patients with cSDH [odds ratio, 0.368; 95% confidence interval (CI), 0.178-0.759; P = 0.007; I 2 = 0%]. The complication rate was also significantly lower in the endoscope-assisted group (OR, 0.249; 95% CI, 0.07-0.882; P = 0.031; I 2 = 71.87%). Conclusion: We conducted the first meta-analysis of endoscope-assisted surgery for cSDH. The meta-analysis of four studies comprising 441 patients with cSDH suggests a significantly decreased risk of recurrence and postoperative complications after endoscope-assisted surgery. Therefore, endoscope-assisted surgery is effective and safe in treating cSDH.

13.
Onco Targets Ther ; 13: 11755-11768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33239887

RESUMO

Purpose: Glioblastoma (GBM) is the most lethal primary cancer in adult central nervous system, and new strategies are desperately needed. The secretory pathway kinase or kinase-like proteins (SPKKPs) have been shown to mediate multiple physiological functions by phosphorylating extracellular proteins and proteoglycans. However, their roles in cancers, especially GBM, remain poorly defined. Methods: The least absolute shrinkage and selection operator (LASSO) regression was employed for establishing the SPKKPs signature for IDH wild type (wt) GBM prognosis. Integrative analyses with multiple datasets were employed to identify the core member of this gene family in glioma. The receiver operator characteristic (ROC) curves and immunohistochemistry were further used for evaluating its association with progressive malignancy in glioma and GBM patients' survival, respectively. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to interpret its functions in GBM, which were further verified in vitro. Results: A SPKKPs classifier was constructed with 3 genes of this family. This signature could effectively distinguish IDH wt GBM survival. Family with sequence similarity 20 C (FAM20C) was further identified as the core member of this family in glioma. Elevated FAM20C expression was not only closely correlated with glioma malignancy progression and the mesenchymal subtype of GBM but also indicated unfavorable survival of GBM patients. FAM20C was also found to be associated with the disrupted immune response in GBM microenvironment and was required for the migration of glioma and immune cells. Conclusion: These data indicate that the potential of FAM20C serving as a predictive molecule and a therapeutic target for GBM.

14.
Front Oncol ; 10: 569584, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194658

RESUMO

Glioma is the most prevalent primary brain tumor in adults and has an extremely unfavorable prognosis. As a member of the lysyl oxidase (LOX) family, lysyl-oxidase-like-2 (LOXL2) is known to play different roles in different tumors. However, the role of LOXL2 in glioma has not yet been fully elucidated. In the present study, we detected that LOXL2 was considerably upregulated in glioma and that LOXL2 upregulation was evidently related to glioma WHO grade, malignant molecular subtypes, and poor prognosis in glioma patients. Additionally, we found that LOXL2 not only promoted glioma cells proliferation, migration, invasion, and induced the epithelial-to-mesenchymal transition (EMT) process, but also reduced the sensitivity of glioma cells to temozolomide (TMZ). Furthermore, we identified that LOXL2 reduced TMZ sensitivity and induced EMT in glioma via the activation of autophagy. Mechanistically, LOXL2 enhanced Atg7 expression by promoting the phosphorylation of Erk1/2, leading to the activation of autophagy and regulation of EMT process and TMZ sensitivity through autophagy. Our study describes an LOXL2-Erk1/2-Atg7 signaling axis that influences glioma EMT and chemosensitivity through autophagy; moreover, LOXL2 may serve as a promising therapeutic target in the treatment of glioma.

15.
Front Oncol ; 10: 581197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194713

RESUMO

Background: Abnormal redox equilibrium is a major contributor to tumor malignancy and treatment resistance. Understanding reactive oxygen species (ROS) metabolism is a key to clarify the tumor redox status. However, we have limited methods to evaluate ROS in tumor tissues and little knowledge on ROS metabolism across human cancers. Methods: The Cancer Genome Atlas multi-omics data across 22 cancer types and the Genomics of Drug Sensitivity in Cancer data were analyzed in this study. Cell viability testing and xenograft model were used to validate the role of ROS modulation in regulating treatment efficacy. Results: ROS indexes reflecting ROS metabolic balance in five dimensions were developed and verified. Based on the ROS indexes, we conducted ROS metabolic landscape across 22 cancer types and found that ROS metabolism played various roles in different cancer types. Tumor samples were classified into eight ROS clusters with distinct clinical and multi-omics features, which was independent of their histological origin. We established a ROS-based drug efficacy evaluation network and experimentally validated the predicted effects, suggesting that modulating ROS metabolism improves treatment sensitivity and expands drug application scopes. Conclusion: Our study proposes a new method in evaluating ROS status and offers comprehensive understanding on ROS metabolic equilibrium in human cancers, which provide practical implications for clinical management.

16.
Cancer Lett ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33166616

RESUMO

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.

17.
J Transl Med ; 18(1): 378, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028341

RESUMO

BACKGROUND: Molecular classification has laid the framework for exploring glioma biology and treatment strategies. Pro-neural to mesenchymal transition (PMT) of glioma is known to be associated with aggressive phenotypes, unfavorable prognosis, and treatment resistance. Recent studies have highlighted that long non-coding RNAs (lncRNAs) are key mediators in cancer mesenchymal transition. However, the relationship between lncRNAs and PMT in glioma has not been systematically investigated. METHODS: Gene expression profiles from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, and Rembrandt with available clinical and genomic information were used for analyses. Bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), Cox analysis, and least absolute shrinkage and selection operator (LASSO) analysis were performed. RESULTS: According to PMT scores, we confirmed that PMT status was positively associated with risky behaviors and poor prognosis in glioma. The 149 PMT-related lncRNAs were identified by WGCNA analysis, among which 10 (LINC01057, TP73-AS1, AP000695.4, LINC01503, CRNDE, OSMR-AS1, SNHG18, AC145343.2, RP11-25K21.6, RP11-38L15.2) with significant prognostic value were further screened to construct a PMT-related lncRNA risk signature, which could divide cases into two groups with distinct prognoses. Multivariate Cox regression analyses indicated that the signature was an independent prognostic factor for high-grade glioma. High-risk cases were more likely to be classified as the mesenchymal subtype, which confers enhanced immunosuppressive status by recruiting macrophages, neutrophils, and regulatory T cells. Moreover, six lncRNAs of the signature could act as competing endogenous RNAs to promote PMT in glioblastoma. CONCLUSIONS: We profiled PMT status in glioma and established a PMT-related 10-lncRNA signature for glioma that could independently predict glioma survival and trigger PMT, which enhanced immunosuppression.

18.
J Transl Med ; 18(1): 327, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867782

RESUMO

BACKGROUND: This study was intended to investigate the genomic landscape of the immune microenvironments of brain metastases in breast cancer. METHODS: Three gene expression profile datasets (GSE76714, GSE125989 and GSE43837) of breast cancer with brain metastases were downloaded from Gene Expression Omnibus (GEO) database. After differential expression analysis, the tumor immune microenvironment and immune cell infiltration were analyzed. Then immune-related genes were identified, followed by function analysis, transcription factor (TF)-miRNA-mRNA co-regulatory network analysis, and survival analysis of metastatic recurrence. RESULTS: The present results showed that the tumor immune microenvironment in brain metastases was immunosuppressed compared with primary caner. Compared with primary cancer samples, the infiltration ratio of plasma cells in brain metastases samples was significantly higher, while the infiltration ratio of macrophages M2 cells in brain metastases samples was significantly lower. Total 42 immune-related genes were identified, such as THY1 and NEU2. CD1B, THY1 and DOCK2 were found to be implicated in the metastatic recurrence of breast cancer. CONCLUSIONS: Targeting macrophages or plasma cells may be new strategies for immunotherapy of breast cancer with brain metastases. THY1 and NEU2 may be potential therapeutic targets for breast cancer with brain metastases, and THY1, CD1B and DOCK2 may serve as potential prognostic markers for improvement of brain metastases survival.

19.
J Pathol ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991738

RESUMO

Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a target for disease prevention. However, the relationship between ACE2 expression and its clinical implications in SARS-CoV-2 pathogenesis remains unknown. Here, we explored the location and expression of ACE2, and its correlation with gender, age, and cigarette smoke (CS), in a CS-exposed mouse model and 224 non-malignant lung tissues (125 non-smokers, 81 current smokers, and 18 ex-smokers) by immunohistochemistry. Moreover, the correlations of ACE2 with CS-induced oxidative stress-related markers, hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and 4-hydroxynonenal (4-HNE) were investigated. Chromatin immunoprecipitation and luciferase reporter assays identified the cause of ACE2 overexpression in human primary lung epithelial cells. We demonstrated that ACE2 was predominantly overexpressed on the apical surface of bronchial epithelium, while reduced in alveolar epithelium, owing to the dramatically decreased abundance of alveolar type II pneumocytes in CS-exposed mouse lungs. Consistent with this, ACE2 was primarily significantly overexpressed in human bronchial and alveolar epithelial cells in smokers regardless of age or gender. Decreased ACE2 expression was observed in bronchial epithelial cells from ex-smokers compared with current smokers, especially in those who had ceased smoking for more than 10 years. Moreover, ACE2 expression was positively correlated with the levels of HIF-1α, iNOS, and 4-HNE in both mouse and human bronchioles. The results were further validated using a publicly available dataset from The Cancer Genome Atlas (TCGA) and our previous integrated data from Affymetrix U133 Plus 2.0 microarray (AE-meta). Finally, our results showed that HIF-1α transcriptionally upregulates ACE2 expression. Our results indicate that smoking-induced ACE2 overexpression in the apical surface of bronchial epithelial cells provides a route by which SARS-CoV-2 enters host cells, which supports clinical relevance in attenuating the potential transmission risk of COVID-19 in smoking populations by smoking cessation. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

20.
Cancer Cell Int ; 20: 419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32874133

RESUMO

Background and aims: Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. Methods: Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein-protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database. Results: A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM. Conclusions: Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.

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