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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38770717

RESUMO

Drug therapy is vital in cancer treatment. Accurate analysis of drug sensitivity for specific cancers can guide healthcare professionals in prescribing drugs, leading to improved patient survival and quality of life. However, there is a lack of web-based tools that offer comprehensive visualization and analysis of pancancer drug sensitivity. We gathered cancer drug sensitivity data from publicly available databases (GEO, TCGA and GDSC) and developed a web tool called Comprehensive Pancancer Analysis of Drug Sensitivity (CPADS) using Shiny. CPADS currently includes transcriptomic data from over 29 000 samples, encompassing 44 types of cancer, 288 drugs and more than 9000 gene perturbations. It allows easy execution of various analyses related to cancer drug sensitivity. With its large sample size and diverse drug range, CPADS offers a range of analysis methods, such as differential gene expression, gene correlation, pathway analysis, drug analysis and gene perturbation analysis. Additionally, it provides several visualization approaches. CPADS significantly aids physicians and researchers in exploring primary and secondary drug resistance at both gene and pathway levels. The integration of drug resistance and gene perturbation data also presents novel perspectives for identifying pivotal genes influencing drug resistance. Access CPADS at https://smuonco.shinyapps.io/CPADS/ or https://robinl-lab.com/CPADS.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Internet , Neoplasias , Software , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biologia Computacional/métodos , Bases de Dados Genéticas , Transcriptoma , Perfilação da Expressão Gênica/métodos
2.
PLoS Comput Biol ; 20(5): e1012024, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38717988

RESUMO

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.


Assuntos
Biomarcadores Tumorais , Biologia Computacional , Bases de Dados Genéticas , Internet , Neoplasias , Software , Humanos , Neoplasias/genética , Neoplasias/mortalidade , Análise de Sobrevida , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Prognóstico , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética
3.
Mol Cancer ; 23(1): 58, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515134

RESUMO

Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.


Assuntos
Neoplasias , Linfócitos T Citotóxicos , Humanos , Epigênese Genética , Neoplasias/metabolismo , Imunoterapia , Biomarcadores/metabolismo
4.
Cancer Sci ; 115(6): 1820-1833, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38571294

RESUMO

Radiotherapy, one of the most fundamental cancer treatments, is confronted with the dilemma of treatment failure due to radioresistance. To predict the radiosensitivity and improve tumor treatment efficiency in pan-cancer, we developed a model called Radiation Intrinsic Sensitivity Evaluation (RISE). The RISE model was built using cell line-based mRNA sequencing data from five tumor types with varying radiation sensitivity. Through four cell-derived datasets, two public tissue-derived cohorts, and one local cohort of 42 nasopharyngeal carcinoma patients, we demonstrated that RISE could effectively predict the level of radiation sensitivity (area under the ROC curve [AUC] from 0.666 to 1 across different datasets). After the verification by the colony formation assay and flow cytometric analysis of apoptosis, our four well-established radioresistant cell models successfully proved higher RISE values in radioresistant cells by RT-qPCR experiments. We also explored the prognostic value of RISE in five independent TCGA cohorts consisting of 1137 patients who received radiation therapy and found that RISE was an independent adverse prognostic factor (pooled multivariate Cox regression hazard ratio [HR]: 1.84, 95% CI 1.39-2.42; p < 0.01). RISE showed a promising ability to evaluate the radiotherapy benefit while predicting the prognosis of cancer patients, enabling clinicians to make individualized radiotherapy strategies in the future and improve the success rate of radiotherapy.


Assuntos
Neoplasias , Tolerância a Radiação , Humanos , Tolerância a Radiação/genética , Prognóstico , Neoplasias/radioterapia , Neoplasias/genética , Neoplasias/patologia , Linhagem Celular Tumoral , Feminino , Masculino , Apoptose/efeitos da radiação , Pessoa de Meia-Idade , Curva ROC , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia
5.
Brief Bioinform ; 23(3)2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35395670

RESUMO

Immune checkpoint inhibitors (ICIs) have completely changed the approach pertaining to tumor diagnostics and treatment. Similarly, immunotherapy has also provided much needed data about mutation, expression and prognosis, affording an unprecedented opportunity for discovering candidate drug targets and screening for immunotherapy-relevant biomarkers. Although existing web tools enable biologists to analyze the expression, mutation and prognostic data of tumors, they are currently unable to facilitate data mining and mechanism analyses specifically related to immunotherapy. Thus, we effectively developed our own web-based tool, called Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer (CAMOIP), in which we are able to successfully screen various prognostic markers and analyze the mechanisms involved in biomarker expression and function, as well as immunotherapy. The analyses include information relevant to survival analysis, expression analysis, mutational landscape analysis, immune infiltration analysis, immunogenicity analysis and pathway enrichment analysis. This comprehensive analysis of biomarkers for immunotherapy can be carried out by a click of CAMOIP, and the software should greatly encourage the further development of immunotherapy. CAMOIP provides invaluable evidence that bridges the information between the data of cancer genomics based on immunotherapy, providing comprehensive information to users and assisting in making the value of current ICI-treated data available to all users. CAMOIP is available at https://www.camoip.net.


Assuntos
Biomarcadores Tumorais , Neoplasias , Biomarcadores Tumorais/genética , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética
6.
J Transl Med ; 22(1): 293, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509593

RESUMO

Regulatory T cells (Tregs) expressing the transcription factor FoxP3 are essential for maintaining immunological balance and are a significant component of the immunosuppressive tumor microenvironment (TME). Single-cell RNA sequencing (ScRNA-seq) technology has shown that Tregs exhibit significant plasticity and functional diversity in various tumors within the TME. This results in Tregs playing a dual role in the TME, which is not always centered around supporting tumor progression as typically believed. Abundant data confirms the anti-tumor activities of Tregs and their correlation with enhanced patient prognosis in specific types of malignancies. In this review, we summarize the potential anti-tumor actions of Tregs, including suppressing tumor-promoting inflammatory responses and boosting anti-tumor immunity. In addition, this study outlines the spatial and temporal variations in Tregs function to emphasize that their predictive significance in malignancies may change. It is essential to comprehend the functional diversity and potential anti-tumor effects of Tregs to improve tumor therapy strategies.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Neoplasias/terapia , Microambiente Tumoral , Imunoterapia/métodos
7.
Plant Physiol ; 193(3): 1849-1865, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37477940

RESUMO

Fruit color is a very important external commodity factor for consumers. Compared to the most typical red octoploid strawberry (Fragaria × ananassa), the pink strawberry often sells for a more expensive price and has a higher economic benefit due to its outstanding color. However, few studies have examined the molecular basis of pink-colored strawberry fruit. Through an EMS mutagenesis of woodland strawberry (Fragaria vesca), we identified a mutant with pink fruits and green petioles. Bulked-segregant analysis sequencing analysis and gene function verification confirmed that the responsible mutation resides in a gene encoding flavanone-3-hydroxylase (F3H) in the anthocyanin synthesis pathway. This nonsynonymous mutation results in an arginine-to-histidine change at position 130 of F3H. Molecular docking experiments showed that the arginine-to-histidine mutation results in a reduction of intermolecular force-hydrogen bonding between the F3H protein and its substrates. Enzymatic experiments showed a greatly reduced ability of the mutated F3H protein to catalyze the conversion of the substrates and hence a blockage of the anthocyanin synthesis pathway. The discovery of a key residue in the F3H gene controlling anthocyanin synthesis provides a clear target of modification for the molecular breeding of strawberry varieties with pink-colored fruits, which may be of great commercial value.


Assuntos
Flavanonas , Fragaria , Antocianinas/genética , Antocianinas/metabolismo , Fragaria/genética , Fragaria/metabolismo , Frutas/genética , Frutas/metabolismo , Histidina/genética , Histidina/metabolismo , Simulação de Acoplamento Molecular , Oxigenases de Função Mista/metabolismo , Mutação/genética , Flavanonas/metabolismo
8.
Br J Surg ; 111(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38055899

RESUMO

BACKGROUND: Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS: Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS: A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS: This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.


Assuntos
Neoplasias Pulmonares , Segunda Neoplasia Primária , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Humanos , Incidência , Segunda Neoplasia Primária/epidemiologia , Inquéritos Nutricionais , Neoplasias da Próstata/epidemiologia , Estudos Retrospectivos , Fatores de Risco
9.
J Med Internet Res ; 26: e54607, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38764297

RESUMO

This study evaluated the capabilities of the newly released ChatGPT-4V, a large language model with visual recognition abilities, in interpreting electrocardiogram waveforms and answering related multiple-choice questions for assisting with cardiovascular care.


Assuntos
Eletrocardiografia , Eletrocardiografia/métodos , Inteligência Artificial
10.
Mol Cancer ; 22(1): 31, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36793048

RESUMO

As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, γδT cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that γδT cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of γδT cells in the tumor microenvironment (TME) and exert antitumor effects by improving γδT-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of γδT cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with γδT cells as a good treatment option.


Assuntos
Neoplasias , Linfócitos T , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imunoterapia , Microambiente Tumoral
11.
Int J Cancer ; 152(3): 480-495, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36274626

RESUMO

Immune checkpoint inhibitors (ICIs) combined with the anti-angiogenesis drug bevacizumab is one of the future directions of immunotherapy. However, the potential adverse drug reactions (ADRs) caused by combination therapy remain unclear. Current research on ADRs of combination therapy in cancer patients is extremely limited. Our study aims to help determine the safety of combination therapy. We downloaded the ADR reports on combination therapy, from the first quarter of 2012 to the fourth quarter of 2021, from the FDA adverse event reporting system (FAERS) database and conducted a large-scale retrospective study. The ADR signals were monitored by reporting odds ratio (ROR) and analyzing the risk of different ADRs in patients with Pan-cancer. A total of 2094 cases were selected, after excluding duplicate data and the use of chemotherapy drugs. We evaluated the risk of ADR in Pan-cancer patients. Combination therapy was an independent risk factor for adverse drug reactions associated with interstitial lung disease (OR: 8.62; 95% CI: 6.14-12.10, P < .0001), hypertension (OR: 1.35; 95% CI: 1.11-1.65, P < .01) and gastrointestinal bleeding (OR: 3.16; 95% CI: 2.21-4.51, P < .0001). A subgroup analysis revealed that the risk of endocrine system-related ADRs was elevated in patients receiving different combination therapies or with certain tumor types. We retrospectively studied the ADR of combination therapy in Pan-cancer patients and analyzed the distribution characteristics of ADR from the perspectives of treatment strategy and cancer types to provide recommendations for the individualized management of patients receiving combination therapy.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Humanos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , Bevacizumab/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico
12.
Nano Lett ; 22(1): 508-516, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34968071

RESUMO

Uricase-based therapies are limited for gout partially due to the accumulation of H2O2 in an arthrosis environment with slow metabolism. To tackle this limitation, previous studies adopted a cascade reaction between the degradation of uric acid (UA) and timely elimination of H2O2 using complicated composites of uricase and catalase (CAT)/CAT-like nanozyme. Herein, the self-cascade nanozyme Pt/CeO2 with high efficiency toward simultaneous UA degradation and H2O2 elimination is demonstrated on the basis of both uricase- and CAT-like activities in Pt, Ir, Rh, and Pd platinum-group metals. With an optimized molar ratio of Pt and CeO2, Pt/CeO2 (1/5) not only does better in degrading UA but also has excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging activities. In monosodium urate (MSU)-induced acute gout rats, Pt/CeO2 nanozyme markedly alleviates pain along with joint edema, thus improving gait claudication and tissue inflammation. These results provide novel insights into strategies of an efficient enzyme-mimetic treatment for gout.


Assuntos
Catalase , Terapia Enzimática , Gota , Urato Oxidase , Animais , Catalase/uso terapêutico , Gota/tratamento farmacológico , Peróxido de Hidrogênio/metabolismo , Ratos , Urato Oxidase/uso terapêutico , Ácido Úrico/metabolismo
13.
Anal Chem ; 94(30): 10636-10642, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35758679

RESUMO

Developing a universal strategy to measure catalase (CAT)/CAT-like activity, on one hand, overcomes limitations on current assays, such as moderate sensitivity and limited sample scope; on the other hand, facilitates insightful studies on applications of CAT and CAT-like nanozymes. Herein, the oxygen-sensitive and H2O2-inhibitory self-polymerization of dopamine (DA) was demonstrated as an activity indicator of CAT or CAT-like nanozymes, which monitors the catalytically generated O2 in a hypoxic environment. A typical assay for natural CAT was achieved under the optimized conditions. Moreover, this assay was suitable for diverse types of samples, ranging from nanozymes, animal tissues, to human saliva. By comparing the merits and limitations of common methods, this assay shows all-round advantages in sensitivity, specificity, and versatility, facilitating the formulation of measurement criteria and the development of potential standardized assays for CAT (or CAT-like nanozyme) activity.


Assuntos
Dopamina , Peróxido de Hidrogênio , Animais , Catalase , Humanos , Oxigênio , Espécies Reativas de Oxigênio
14.
Cancer Cell Int ; 22(1): 186, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562800

RESUMO

Immune checkpoint inhibitors (ICIs) have made important breakthrough in anti-tumor therapy, however, no single biomarker can accurately predict their efficacy. Studies have found that tumor microenvironment is a key factor for determining the response to ICI therapy. Cytokine receptor 3 (C-X-C Motif Chemokine Receptor 3, CXCR3) pathway has been reported to play an important role in the migration, activation, and response of immune cells. We analyzed survival data, genomics, and clinical data from patients with metastatic urothelial carcinoma (mUC) who received ICI treatment to explore the relationship between CXCR3 pathway activation and the effectiveness of ICIs. The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort and six other cohorts receiving ICI treatment were used for mechanism exploration and validation. In the ICI cohort, we performed univariate and multivariate COX analyses and discovered that patients in the CXCR3-high group were more sensitive to ICI treatment. A Kaplan-Meier analysis demonstrated that patients in the high CXCR3-high group had a better prognosis than those in the CXCR3-low group (P = 0.0001, Hazard Ratio = 0.56; 95% CI 0.42-0.75). CIBERSORT analysis found that mUC patients in the CXCR3-high group had higher levels of activated CD8+ T cells, M1 macrophages, and activated NK cells and less regulatory T cell (Treg) infiltration. Immunogenicity analysis showed the CXCR3-high group had higher tumor neoantigen burden (TNB). Our study suggests that CXCR3 pathway activation may be a novel predictive biomarker for the effectiveness of immunotherapy in mUC patients.

15.
Cancer Cell Int ; 22(1): 173, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488336

RESUMO

The characterization of immunological and genomic differences in small-cell lung cancer (SCLC) between East Asian (EA) and Caucasian patients can reveal important clinical therapies for EA patients with SCLC. By sequencing and analyzing a molecular and immunological dataset of 98-SCLC patients of EA ancestry, immunogenicity, including DNA damage repair alterations and tumor mutation burden (TMB), was found to be significantly higher in the EA cohort than in the Caucasian cohort. The epithelial-mesenchymal transition (EMT) was the signaling signature with the predominant frequency of mutations across all patients in the EA cohort. Analysis of tumor-infiltrated immune cells revealed that resting lymphocytes were significantly enriched in the EA cohort. Compound-targeting analysis showed that topoisomerase inhibitors might be capable of targeting TP53 and RB1 comutations in EA SCLC patients. EA SCLC patients who harbored COL6A6 mutations had poor survival, while Caucasian SCLC patients with OTOF, ANKRD30B, and TECPR2 mutations were identified to have a shorter survival.

16.
Cancer Cell Int ; 22(1): 229, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836254

RESUMO

BACKGROUND: Colon adenocarcinoma (COAD) is one of the major varieties of malignant tumors threatening human health today. Immune checkpoint inhibitors (ICIs) have recently begun to emerge as an effective option for the treatment of COAD patients, but not all patients can benefit from ICI treatment. Previous studies have suggested that ICIs boast significant clinical effects on patients with microsatellite instability-high (MSI-H), while conversely patients with microsatellite-stable/microsatellite instability-low (MSS/MSI-L) have shown limited response. METHODS: We used ATAC-seq, RNA-seq, and mutation data from The Cancer Genome Atlas Colon adenocarcinoma (TCGA-COAD) cohort to perform multi-omics differential analysis on COAD samples with different MSI statuses, then further screened genes by additionally combining these results with survival analysis. We analyzed the effects of the screened genes on the tumor microenvironment and immunogenicity of COAD patients, and subsequently determined their influence on the efficacy of ICIs in COAD patients using a series of predictive indexes. RESULTS: Twelve genes were screened in the TCGA-COAD cohort, and after the combined survival analysis, we identified ATOH1 as having significant effects. ATOH1 is characterized by high chromatin accessibility, high expression, and high mutation in COAD patients in the MSI-H group. COAD patients with high ATOH1 expression are associated with a better prognosis, unique immune microenvironment, and higher efficacy in ICI treatment. Enrichment analysis showed that COAD patients with high ATOH1 expression displayed significant upregulation in their humoral immunity and other related pathways. CONCLUSIONS: We speculate that ATOH1 may influence the efficacy of ICIs therapy in patients with COAD by affecting the immune microenvironment and immunogenicity of the tumor.

17.
Anal Chem ; 93(14): 5954-5962, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33797896

RESUMO

Various transition-metal oxide (TMO)-based nanomaterials have been explored as peroxidase mimics. However, the moderate peroxidase-like activity of TMOs limited their widespread use. Decorating highly active noble-metal nanozymes on the surface of TMOs can not only enhance the peroxidase-like activity of TMOs but also prevent the small-sized metal nanoparticles (NPs) from aggregation. Herein, in situ exsolution of noble-metal NPs (i.e., Ir and Ru) from A-site-deficient perovskite oxides (i.e., chemical formula La0.9B0.9B'0.1O3-δ, B = Mn/Fe, B' = Ir/Ru) under a reducing atmosphere was achieved for preparing noble-metal NPs/perovskite composites. The exsolved NPs were socketed on the surface of parent perovskite oxides, which significantly enhanced the stability of metal NPs. In addition, the peroxidase-like activity of perovskite oxides increased remarkably after NPs egress. We then used the optimized Ir/LMIO with high stability and excellent peroxidase-like activity to develop a colorimetric assay for the determination of alkaline phosphatase (ALP). Benefiting from the remarkable peroxidase-like activity of Ir/LMIO, the sensing platform exhibited a wide linear range. The practical application of the colorimetric sensing method was demonstrated by detecting the ALP in serum samples. This work not only provides new insights into the synthesis of highly active peroxidase-like nanozymes but expands their applications for constructing a high-performance biosensing platform.


Assuntos
Nanopartículas Metálicas , Peroxidase , Compostos de Cálcio , Óxidos , Peroxidases , Titânio
18.
Cancer Immunol Immunother ; 70(1): 137-151, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32653938

RESUMO

To date, immunotherapy has opened a new chapter in the treatment of lung cancer. Precise biomarkers can help to screen subpopulations of lung cancer to provide the best treatment. Multiple studies suggest that specific gene mutations may be predictive markers in guiding non-small cell lung cancer (NSCLC) immune checkpoint inhibitor (ICI) treatment. A published immunotherapy cohort with mutational and survival data for 350 NSCLC patients was used. First, the mutational data of the immunotherapy cohort were used to identify gene mutations related to the prognosis of ICI therapy. The immunotherapy cohort and TCGA-NSCLC cohort were further studied to elucidate the relationships between specific gene mutations and tumor immunogenicity, antitumor immune response capabilities, and immune cell and mutation counts in the DNA damage response (DDR) pathway. In the immunotherapy cohort (N = 350), ZFHX3 mutations were an independent predictive biomarker for NSCLC patients receiving ICI treatment. Significant differences were observed between ZFHX3-mutant (ZFHX3-MT) and ZFHX3-wild type (ZFHX3-WT) patients regarding the overall survival (OS) time (P < 0.001, HR = 0.26, 95% Cl 0.17-0.41). ZFHX3-MT is significantly associated with higher tumor mutation burden (TMB) and neoantigen load (NAL), and ZFHX3-MT positively correlates with known immunotherapy response biomarkers, including T-cell infiltration, immune-related gene expression, and mutation counts in the DDR pathway in NSCLC. ZFHX3-MT is closely related to longer OS in NSCLC patients treated with ICIs, suggesting that ZFHX3 mutations be used as a novel predictive marker in guiding NSCLC ICI treatment.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Homeodomínio/genética , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação/genética , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Expressão Gênica/imunologia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Masculino , Mutação/efeitos dos fármacos , Prognóstico
19.
Chemistry ; 27(65): 16181-16188, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34554619

RESUMO

Acquiring desirable device performance with deep-blue color purity that fulfills practical application requirements is still a challenge. Bipolar fluorescent emitters with hybrid local and charge transfer (HLCT) state may serve to address this issue. Herein, by inserting anthracene core in the deep-blue building blocks, the authors successfully developed two highly twisted D-π-A fluorescent emitters, ICz-An-PPI and IP-An-PPI, featuring different acceptor groups. Both exhibited superb thermal stabilities, high photo luminescent quantum yields and excellent bipolar transport capabilities. The non-doped OLEDs using ICz-An-PPI and IP-An-PPI as the emitting layers showed efficient blue emission with an external quantum efficiency (EQEmax ) of 4.32 % and 5.41 %, and the CIE coordinates of (0.147, 0.180) and (0.149, 0.150), respectively. In addition, the deep blue doped device based on ICz-An-PPI was achieved with an excellent CEmax of 5.83 cd A-1 , EQEmax of 4.6 % and the CIE coordinate of (0.148, 0.078), which is extremely close to the National Television Standards Committee (NTSC) standard. Particularly, IP-An-PPI-based doped device had better performance, with an EQEmax of 7.51 % and the CIE coordinate of (0.150, 0.118), which was very impressive among the recently reported deep-blue OLEDs with the CIEy <0.12. Such high performance may be attributed to the hot exciton HLCT mechanism via T7 to S2 . Our work may provide a new approach for designing high-efficiency deep-blue materials.

20.
Analyst ; 146(6): 1872-1879, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33522521

RESUMO

Analyzing the SOD-like activity of nanozymes in vitro is of great importance for identifying new nanozymes and predicting their potential biological effects in vivo. However, false negative or positive results occasionally occur due to the mismatch between the detection methods and nanozymes. Here, five typical SOD-like nanozymes, including CeO2, Mn3O4, Prussian blue (PB), PCN222-Mn, and Pt NPs, have been used to evaluate the sensitivity and accuracy of several commonly used in vitro detection methods. By systematically analyzing the detection results, several precautions have been taken. (1) The hydroethidine (HE) probe could be disturbed by the nanozyme with oxidative ability. (2) The nitro blue tetrazolium (NBT) probe has a moderate sensitivity due to the poor water solubility of its reduced product. (3) The water-soluble tetrazolium salt (WST)-8 probe has a higher sensitivity than both NBT and iodonitrotetrazolium chloride (INT). (4) The detection system using the irradiation of riboflavin to produce ˙O2- might be interfered by the nanozyme with photosensibility. (5) Both the quality of DMPO and incubation time are important factors for electron paramagnetic resonance (EPR) measurement. This study will be useful for choosing more suitable in vitro detection methods of SOD-like activity for nanozymes in the future.


Assuntos
Superóxido Dismutase , Água , Espectroscopia de Ressonância de Spin Eletrônica , Oxirredução , Superóxido Dismutase/metabolismo
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