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1.
Biol Trace Elem Res ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771434

RESUMO

In order to explore the effect of excessive iron supplementation on ferroptosis in mouse testes, Kunming mice received injections of varying concentrations of iron. The organ weight, sperm density, and malformation rate were measured. Observations of pathological and ultrastructural alterations in spermatogenic tubules were conducted using haematoxylin eosin (HE) staining and transmission electron microscopy(TEM). Transcript levels of related genes and serum biochemical indicators were measured in mouse testicular tissue. The results showed that higher iron concentration inhibited the growth of mice; reduced the organ coefficients of the testis, heart, and liver; and increased the rate of sperm malformation and mortality. Supplementation with high levels of iron ions can adversely affect the male reproductive system by reducing sperm count, damaging the structure of the seminiferous tubules and causing sperm cell abnormalities. In addition, the iron levels also affected the immune response and blood coagulation ability by affecting the red blood cells, white blood cells and platelets. The results showed that iron ions can affect mouse testicular tissue and induce ferroptosis by altering the expression of ferroptosis-related genes. However, the degree of effect was different for the different concentrations of iron ions. The study also revealed the potential role of deferoxamine in inhibiting the occurrence of ferroptosis. Nevertheless, the damage caused to the testis by deferoxamine supplementation suggests the need for further research in this direction. This study provides reference for reproductive toxicity induced by environmental iron exposure and clarifies the mechanism of reproductive toxicity caused by iron overload and the important role of iron in the male reproductive system.

2.
Sci Rep ; 14(1): 522, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177255

RESUMO

S-palmitoylases and S-depalmitoylases are differentially expressed in various cancers and several malignant tumors and show a strong prognostic ability. Notwithstanding, the potential clinical impact of S-palmitoylases and S-depalmitoylases, particularly in the prognosis and progression of lung adenocarcinoma (LUAD), has not been clarified. Expression levels of S-palmitoylases and S-depalmitoylases in LUAD were investigated using TCGA. GEPIA was used to evaluate the mRNA levels of S-palmitoylases and S-depalmitoylases at different pathological stages. Metascape was used to investigate the biological significance of S-palmitoylases and S-depalmitoylases. The Kaplan-Meier plotter was used to analyze the prognostic value of S-palmitoylases and S-depalmitoylases. CBioportal was used to analyze gene alterations in S-palmitoylases and S-depalmitoylases. UALCAN was used to examine DNA promoter methylation levels of S-palmitoylases and S-depalmitoylases. Finally, we investigated the relationship between S-palmitoylases, S-depalmitoylases, and tumor-infiltrating immune cells using TIMER. Correlations with immune checkpoint-related genes were determined using the R packages reshape2, ggpubr, ggplot2, and corrplot. PCR was also performed to assess the degree of ZDHHC4/12/18/24 and APT2 transcript expression in lung adenocarcinoma and adjacent normal lung tissues. HPA was utilized to investigate protein levels of S-palmitoylases and S-depalmitoylases in LUAD and normal lung tissue. Our study found that ZDHHC2/3/4/5/6/7/9/12/13/16/18/20/21/23/24, APT1/2, PPT1, LYPLAL1, ABHD4/10/11/12/13 and ABHD17C mRNA expression was significantly upregulated in LUAD, whereas ZDHHC1/8/11/11B/14/15/17/19/22, ABHD6/16A and ABHD17A mRNA expression was significantly downregulated. The functions of the differentially expressed S-palmitoylases and S-depalmitoylases were mainly associated with protein-cysteine S-palmitoyltransferase and protein-cysteine S-acyltransferase activities. Patients with high expression of ZDHHC4/12/18/24, APT2, ABHD4, ABHD11 and ABHD12 had a shorter overall survival. Infiltration of six immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) was closely associated with the expression of ZDHHC4/12/18/24 and APT2. ZDHHC4/12/18/24 and APT2 positively correlated with the immune checkpoint-related gene CD276. We assessed the mRNA levels of ZDHHC4/12/18/24 and APT2 using qRT-PCR and found increased expression of ZDHHC4/12/18/24 in LUAD compared with healty control lung tissues. ZDHHC4/12/18/24, and APT2 are potential prognostic biomarkers of LUAD. Their expression levels could be related to the tumor microenvironment in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Linfócitos T CD8-Positivos , Cisteína , Prognóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , RNA Mensageiro/genética , Biomarcadores , Biomarcadores Tumorais/genética , Microambiente Tumoral , Antígenos B7 , Monoacilglicerol Lipases , Serina Proteases
4.
Int J Gen Med ; 16: 1757-1769, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37193249

RESUMO

Background: Immunotherapy drugs, immune checkpoint inhibitors (ICIs), have been approved for first- and second-line treatment of non-small cell lung cancer (NSCLC), but only a portion of patients respond to ICIs. It is crucial to screen the beneficiaries of immunotherapy through biomarkers accurately. Methods: Several datasets were used to explore the predictive value for immunotherapy and immune relevance of guanylate binding protein 5 (GBP5) in NSCLC, including the GSE126044 dataset, The Cancer Genome Atlas (TCGA) dataset, Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset, the Kaplan-Meier plotter dataset, the HLuA150CS02 cohort, and the HLugS120CS01 cohort. Results: GBP5 was upregulated in tumor tissues but associated with a good prognosis in NSCLC. Moreover, our findings demonstrated that GBP5 was strongly correlated with the expression of many immune-related genes, TIIC levels, and PD-L1 expression based on RNA-seq data onto online databases and validation of the NSCLC tissue microarray using IHC staining. Moreover, pan-cancer analysis has shown that GBP5 was a factor in identifying immuno-hot tumors, except for a few tumor types. Conclusion: In summary, our current research suggests that GBP5 expression is a potential biomarker for predicting the outcome of NSCLC patients treated with ICIs. More research with large-scale samples is needed to determine their value as biomarkers of ICIs benefit.

5.
Clin Immunol ; 246: 109204, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36503156

RESUMO

Formins are evolutionarily conserved genes and profoundly affect cancer progression. This study aims to explore the expressions, prognostic values, and immunological correlations of Formins in cancer. Specific Formins were dysregulated and immuno-biologically correlated in breast cancer (BRCA). Formins showed different expression patterns, namely some were enriched in immune cells while some were enriched in tumor cells. Among all Formins, DIAPH1 was enriched in tumor cells and associated with an inflamed tumor microenvironment (TME). DIAPH1 functioned as an oncogene in BRCA and mediated TGF-ß1-induced epithelial-mesenchymal transformation (EMT) and PD-L1 expression. Moreover, DIAPH1 was overexpressed in most cancers and functioned as a novel pan-cancer immuno-marker, which could predict the response to anti-PD-1/PD-L1 immunotherapy. Overall, DIAPH1 functions as an oncogene and is immunologically correlated, which could be utilized as an alternative biomarker for predicting the immunotherapeutic response.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Forminas , Neoplasias/tratamento farmacológico , Prognóstico , Imunoterapia , Microambiente Tumoral
6.
Front Cell Infect Microbiol ; 13: 1303456, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38162581

RESUMO

Background: Co-infection has been a significant contributor to morbidity and mortality in previous influenza pandemics. However, the current influenza A (H1N1) pdm09 virus pandemic, as the first major outbreak following the SARS-CoV-2 pandemic, may differ epidemiologically. Further investigation is necessary to understand the specific features and impact of this influenza A pandemic. Study design: We conducted a retrospective cohort study at a Chinese hospital between January and April 2023, focusing on patients with lower respiratory tract infections. Pathogen detection employed targeted next-generation sequencing (tNGS) on bronchoalveolar lavage fluid (BALF) or sputum samples. Results: This study enrolled 167 patients with lower respiratory tract infections, and the overall positivity rate detected through tNGS was around 80%. Among them, 40 patients had influenza A (H1N1) pdm09 virus infection, peaking in March. In these patients, 27.5% had sole infections, and 72.5% had co-infections, commonly with bacteria. The frequently detected pathogens were Aspergillus fumigatus, SARS-CoV-2, and Streptococcus pneumoniae. For non-influenza A virus-infected patients, the co-infection rate was 36.1%, with 42.3% having SARS-CoV-2. Patients with influenza A virus infection were younger, had more females and diabetes cases. Among them, those with sole infections were older, with less fever and asthma but more smoking history. Regarding prognosis, compared to sole influenza A virus infection, co-infected patients demonstrated higher 21-day recovery rates and a higher incidence of heart failure. However, they exhibited lower proportions of respiratory failure, acute kidney failure, septic shock, and hospital stays lasting more than 10 days. Interestingly, patients with non-influenza A virus infection had a significantly lower 21-day recovery rate. Correlation analysis indicated that the 21-day recovery rate was only associated with influenza A (H1N1) pdm09 virus. Conclusion: During the current pandemic, the influenza A (H1N1) pdm09 virus may have been influenced by the SARS-CoV-2 pandemic and did not exhibit a strong pathogenicity. In fact, patients infected with influenza A virus showed better prognoses compared to those infected with other pathogens. Additionally, tNGS demonstrated excellent detection performance in this study and showed great potential, prompting clinical physicians to consider its use as an auxiliary diagnostic tool.


Assuntos
Coinfecção , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções Respiratórias , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Coinfecção/epidemiologia , Coinfecção/complicações , Estudos Retrospectivos , Infecções Respiratórias/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala
7.
Front Pharmacol ; 13: 1025921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313290

RESUMO

It has been well-defined that tumor-infiltrating lymphocytes (TILs) play critical roles in pancreatic cancer (PaCa) progression. This research aimed to comprehensively explore the composition of TILs in PaCa and their potential clinical significance. A total of 178 samples from the TCGA and 63 samples from the GSE57495 dataset were enrolled in our study. ImmuCellAI was applied to calculate the infiltrating abundance of 24 immune cell types in PaCa and further survival analysis revealed the prognostic values of TILs in PaCa. Moreover, the Hallmark enticement analysis of differentially expressed genes (DEGs) between low- and high-risk groups was performed as well. Immunohistochemistry staining was used to evaluate NEUROD1 expression. As result, different kinds of TILs had distinct infiltrating features. In addition, Specific TILs subsets had notable prognostic values in PaCa. We further established a 6-TILs signature to assess the prognosis of PaCa patients. Kaplan-Meier and Cox regression analyses both suggested the significant prognostic value of the signature in PaCa. Based on the prognostic signature, we screened a great deal of potential prognostic biomarkers and successfully validated NEUROD1 as a novel prognostic biomarker in PaCa. Overall, the current study illuminated the immune cells infiltrating the landscape in PaCa and identified a TILs-dependent signature and NEUROD1 for prognostic prediction in PaCa patients.

8.
Heliyon ; 8(10): e11083, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36281404

RESUMO

Background: As a common malignant disease in females, breast cancer (BCa) causes increasing numbers of cancer-related death. Collagen X alpha 1 chain (COL10A1) plays a critical role in the oncogenesis and progression of malignant tumors. However, a systematic analysis of COL10A1 in BCa has not been conducted. Methods: The COL10A1 expression level and prognostic value in BCa were defined through the Cancer Genome Atlas (TCGA) as well as the Kaplan-Meier plotter data respectively. The expression pattern of COL10A1 was subsequently confirmed on tissue microarray (TMA) by immunochemistry (IHC) staining. Moreover, cellular functional assays which aimed to evaluate cell proliferation, migration, invasion, and apoptosis, were conducted to investigate the oncogenic activity of COL10A1 in BCa. Then, Tumor Immune Estimation Resource (TIMER) was adopted to determine the association between COL10A1 expression and immune cell infiltration. Results: Bioinformatics analysis revealed that COL10A1 was significantly overexpressed and had notable prognostic value, especially for distant metastasis-free survival (DMFS) in BCa. Moreover, IHC analysis of 140 BCa tissues on TMA chips exhibited the overexpression of COL10A1 was correlated to advanced clinical stage, poor overall survival (OS), and worse recurrence-free survival (RFS). Besides, knockdown of COL10A1 remarkably suppressed cell proliferation, migration, and invasion in BCa cells, and notably promoted cell apoptosis as well. Furthermore, COL10A1 was positively associated with immune cell infiltration including B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell. Conclusion: The results revealed that COL10A1 is a novel oncogene and could serve as a potential prognostic biomarker in BCa. Besides, the downregulation of COL10A1 could inhibit BCa progression, which could be a potential target for BCa therapy.

9.
Front Genet ; 13: 969723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159996

RESUMO

With continued advances in cancer research, the crucial role of the tumor microenvironment (TME) in regulating tumor progression and influencing immunotherapy outcomes has been realized over the years. A series of studies devoted to enhancing the response to immunotherapies through exploring efficient predictive biomarkers and new combination approaches. The microfluidic technology not only promoted the development of multi-omics analyses but also enabled the recapitulation of TME in vitro microfluidic system, which made these devices attractive across studies for optimization of immunotherapy. Here, we reviewed the application of microfluidic systems in modeling TME and the potential of these devices in predicting and monitoring immunotherapy effects.

10.
Int J Gen Med ; 15: 7383-7393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36164284

RESUMO

Purpose: The aim of this study was to explore the clinical significance of deglycosylated PD-L1 level and its correlation with EGFR and ALK mutation in lung adenocarcinoma. Materials and Methods: We estimated the intensity of both native and deglycosylated PD-L1 signals using a 28-8 antibody on lung adenocarcinoma tissue microarray sections. We analyzed the difference in the H-score between tumor and paratumor tissues, as well as that before and after deglycosylation. Correlations between EGFR or ALK status and PD-L1 expression were analyzed. We also evaluated the differences among survival curves. Results: The expression level of PD-L1 in lung adenocarcinoma tissues was significantly higher than that in paratumor tissues (P<0.0001). Deglycosylation significantly enhanced the detection of PD-L1 in tumor tissues (P<0.0001). There was no statistical significance between the signal intensity of deglycosylated PD-L1 and the survival of patients (P=0.9099). However, the response to deglycosylation of PD-L1 was significantly correlated with the survival of patients with stage N1-N3 (P=0.0435) and stage T3-T4 (P=0.0366) and male patients (P=0.0258). A statistical trend was found in the correlation between the response to deglycosylation of PD-L1 and the survival of patients with grade II-III plus grade III (P=0.0973). Correlation between EGFR or ALK status and the expression of PD-L1 was not found (P>0.05). Conclusion: PD-L1 deglycosylation enhances the detection of PD-L1 when utilizing a 28-8 antibody. Moreover, the response to deglycosylation of PD-L1 may predict the survival of certain patients with lung adenocarcinoma.

12.
ACS Nano ; 16(1): 855-868, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35025200

RESUMO

Ferroptosis, resulting from the catastrophic accumulation of lipid reactive oxygen species (ROS) and the inactivation of glutathione (GSH)-dependent peroxidase 4 (GPX4), has emerged as a form of regulated cell death for cancer therapy. Despite progress made with current ferroptosis inducers, efficient systems to trigger ferroptosis remain challenging, owing largely to their low activity, uncontrollable behavior, and even nonselective interactions. Here, we report a self-adaptive ferroptosis platform by engineering a DNA modulator onto the surface of single-atom nanozymes (SAzymes). The modulator could not only specifically intensify the ROS-generating activity but also endow the SAzymes with on-demand GSH-consuming ability in tumor cells, accelerating selective and safe ferroptosis. The self-adaptive antitumor response has been demonstrated in colon cancer and breast cancer, promoting the development of selective cancer therapy.


Assuntos
Neoplasias da Mama , Ferroptose , Humanos , Feminino , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral
13.
Technol Cancer Res Treat ; 20: 15330338211011970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33955303

RESUMO

BACKGROUND: Immune checkpoints play crucial roles in the immune escape of cancer cells. However, the exact prognostic values of expression and methylation of programmed-death 1 (PD-1), programmed-death-ligand 1 (PD-L1) and PD-L2 in low-grade glioma (LGG) have not been well-defined yet. METHODS: A total 514 LGG samples from the Cancer Genome Atlas (TCGA) dataset containing gene expression, DNA methylation, and survival data were enrolled in our study. Besides, a total of 137 primary LGG samples from the Chinese Glioma Genome Atlas (CGGA) database were also extracted for the survival analysis of the prognostic values of PD-1/PD-Ls expression. RESULTS: PD-1/PD-Ls had distinct co-expression patterns in LGG tissues. The expression and methylation level of PD-1/PD-Ls seemed to be various in different LGG subtypes. Besides, overexpression and hypo-methylation of PD-1/PD-Ls were associated with worse prognosis. In addition, PD-1/PD-Ls expression was positively associated with TIICs infiltration, while their methylation was negatively associated with TIICs infiltration. Moreover, PD-1/PD-Ls and their positively correlated gene mainly participated in immune response related biological processes. CONCLUSION: To conclude, overexpression and hypo-methylation of PD-1/PD-Ls predicted unfavorable prognosis in LGG patients, suggesting those patients may benefit from PD1/PD-Ls checkpoint inhibitors treatment.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/imunologia , Glioma/metabolismo , Humanos , Linfócitos do Interstício Tumoral/imunologia , Mutação , Prognóstico , Proteína 2 Ligante de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/genética , Taxa de Sobrevida , Células Tumorais Cultivadas
14.
Medicine (Baltimore) ; 100(17): e25622, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907116

RESUMO

OBJECTIVES: To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS: Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION: This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.


Assuntos
Miastenia Gravis/terapia , Plasmaferese/métodos , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Ensaios Clínicos Controlados não Aleatórios como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
15.
BMC Vet Res ; 17(1): 114, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678162

RESUMO

BACKGROUND: Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study. RESULTS: After infection with the HPI+/HPI- strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI+/HPI--infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and GSDMD, with significantly higher levels detected in the HPI+ group compared to those in the HPI- group (P < 0.01 or P < 0.05). HPI+ strain is more pathogenic than HPI- strain. CONCLUSION: Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1ß and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.


Assuntos
Escherichia coli/patogenicidade , Ilhas Genômicas , Macrófagos/microbiologia , Piroptose , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 1/metabolismo , Linhagem Celular , Membrana Celular/patologia , China , Escherichia coli/genética , Regulação da Expressão Gênica , Inflamação , Lipopolissacarídeos/farmacologia , Macrófagos/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Suínos
16.
Pathol Res Pract ; 219: 153348, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33540373

RESUMO

Despite the rapid development of novel adjuvant and neoadjuvant chemotherapeutic drugs in recent years, advanced ovarian cancer still lacks effective treatment strategies and remains one of the main causes of death among women. Wnt protein family is widely expressed in a variety of human tissues, and Wnt5a is an important member of the noncanonical Wnt pathway. Wnt5a has been found to induce tumor suppression as well as to function as an oncogene depending upon the specific cancer type. In ovarian cancer, Wnt5a protein expression has been observed to be significantly upregulated and associated with poor prognosis. Researchers found that downregulating Wnt5a expression levels effectively suppresses ovarian cancer cell migration and invasion abilities. We believe that the downregulation of Wnt5a will be an attractive and promising antimetastatic therapeutic approach for the future treatment of patients with advanced ovarian cancer. The present review focuses on the mechanisms and therapeutic potential of Wnt5a as a promising novel therapeutic target for ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Proteína Wnt-5a/metabolismo , Carcinoma Epitelial do Ovário/genética , Movimento Celular/fisiologia , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas/genética , Transdução de Sinais/fisiologia , Proteína Wnt-5a/genética
17.
Mol Cancer ; 20(1): 11, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413365

RESUMO

Emerging evidence has revealed that the removal of N-linked glycosylation could enhance PD-L1 detection. However, whether PD-L1 antibodies against different epitopes of PD-L1 antigens responding to deglycosylation has not been characterized. In this study, we compared natural and deglycosylated PD-L1 expression in lung cancer (LuCa) using a panel of PD-L1 antibodies (28-8, CAL10, 73-10 and SP142). We found that removal of N-linked glycosylation markedly enhanced PD-L1 detection when the 28-8, CAL10 and SP142 monoclonal antibodies (mAbs) were used but slightly inhibited PD-L1 detection when the 73-10 mAb was used. Moreover, for the CAL10 and SP142 mAbs, deglycosylated PD-L1 levels showed stronger correlations with the response to anti-PD-1 therapy. Overall, our research provides a comprehensive insight into the application of deglycosylated PD-L1 detection, which expands the clinical significance of this established strategy in LuCa.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/metabolismo , Anticorpos Antineoplásicos/imunologia , Antígeno B7-H1/imunologia , Glicosilação , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
J Cardiothorac Surg ; 15(1): 270, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993739

RESUMO

BACKGROUND: Despite the burgeoning literature describing preoperative and postoperative risks of a myasthenic crisis after thymectomy (MCAT) in patients with myasthenia gravis, substantial differences exist in the risk factors identified by previous studies. We conducted a meta-analysis to assess the reported risk factors and MCAT risk. METHODS: We collected relevant studies on the risk factors for MCAT by searching the PubMed, Embase, The Cochrane Library, China Biology Medicine (CBM), WanFang Data, VIP and CNKI databases. The search period ranged from the establishment of the database to November 2019. RESULTS: Twenty-five of the 458 identified studies were eligible for the meta-analysis. Seven retrospective cohort studies and 18 case-control studies were included, and 14 risk factors for MCAT were extracted. Meta-analyses of the association between MCAT and risk factors related to the patient's preoperative condition included a preoperative history of MC, preoperative bulbar symptoms, IIa + IIb + III + VI, IIb + III + VI, VI + V, dosage of pyridostigmine bromide prior to the operation, a preoperative AchR-Ab level > 100 (nm/L), preoperative pulmonary function, preoperative complications, and preoperative disease course. Meta-analyses of the association between MCAT and surgery-related risk factors included intraoperative blood loss > 1000 mL and the mode of operation. Meta-analyses of the association between MCAT and postoperative risk factors included postoperative lung infection, thymoma and the WHO classification. The operation time was not an independent risk factor for MCAT. CONCLUSIONS: The independent risk factors for MCAT were a preoperative history of MC, preoperative bulbar symptoms, preoperative MG Osserman stage, preoperative dosage of pyridostigmine bromide, preoperative serum AchR-Ab level, lung function, major postoperative complications, disease duration before thymectomy, blood loss, thoracotomy, postoperative lung infection, thymoma, and WHO classification.


Assuntos
Miastenia Gravis/etiologia , Complicações Pós-Operatórias/etiologia , Timectomia/efeitos adversos , Perda Sanguínea Cirúrgica , Bases de Dados Factuais , Feminino , Humanos , Masculino , Miastenia Gravis/patologia , Miastenia Gravis/cirurgia , Duração da Cirurgia , Fatores de Risco , Timectomia/métodos
19.
DNA Cell Biol ; 39(10): 1838-1849, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32876480

RESUMO

The breast cancer gene 1 (BRCA1) is a tumor suppressor, and mutations or epigenetic inactivation will increase the risk of breast cancer oncogenesis. The current research aimed to explore the relationship between BRCA1 expression, prognosis, and tumor immunity in hepatocellular carcinoma (HCC). In this study, BRCA1 expression was analyzed via multiple online databases and its association with clinical characteristics, prognosis and genetic alterations was identified using the original The Cancer Genome Atlas-liver hepatocellular carcinoma cohorts. DNA methylation sites and their prognostic values were analyzed using MethSurv. The correlations between BRCA1 and immune infiltration were investigated via Tumor Immune Estimation Resource. As results, BRCA1 was significantly upregulated in tumor tissues in multiple HCC cohorts. Besides, high BRCA1 expression was correlated with race, advanced T stage, clinical stage, poor tumor grade, MSI status, and worse prognosis. Notably, BRCA1 expression was positively correlated with infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. The current findings imply that BRCA1 is associated with prognosis and immune infiltration, laying foundations for in-depth research on the role of BRCA1 in HCC.


Assuntos
Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Movimento Celular , Metilação de DNA , Células Dendríticas/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Linfócitos/imunologia , Macrófagos/imunologia
20.
Cancer Cell Int ; 20: 265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32587475

RESUMO

Circular RNA (circRNA) is a novel class of regulatory noncoding RNA (ncRNA) molecules with a unique covalently closed loop structure. Next-generation sequencing shows that thousands of circRNAs are widely and stably expressed in multiple eukaryotes. As novel regulatory ncRNAs, circRNAs possess several specific molecular functions, including regulating gene transcription and translation, acting as miRNA sponges, and interacting with functional proteins. Ovarian cancer (OvCa) is one of the most aggressive malignant diseases affecting the lives of thousands of women worldwide, and the majority of OvCa cases are diagnosed at advanced stages. Accumulating evidence has revealed the significant roles of circRNAs in the occurrence and progression of OvCa, indicating the function of circRNAs as promising biomarkers and their therapeutic relevance in this disease. This review aims to summarize the mechanisms by which circRNAs mediate OvCa progression as well as their diagnostic and prognostic values in OvCa.

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