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The sensitive detection of antioxidants in food is essential for the rational control of their usage and reducing potential health risks. A simple three-dimensional (3D) electrode integrated with an anti-fouling/anti-interference layer possesses great potential for the direct and sensitive electrochemical detection of antioxidants in food samples. In this work, a 3D electrochemical sensor was developed by integrating a 3D graphene electrode (3DG) with vertically ordered mesoporous silica film (VMSF), enabling highly sensitive detection of the common antioxidant, butylated hydroxyanisole (BHA), in food samples. A simple electrochemical polarization was employed to pre-activate the 3DG electrode (p3DG), enhancing its hydrophilicity. Using the p3DG as the supporting electrode, stable modification of VMSF was achieved using the electrochemical assisted self-assembly (EASA) method, without the need for any adhesive agents (VMSF/p3DG). Taking BHA in food as a model analyte, the VMSF/p3DG sensor demonstrated high sensitivity, due to the enrichment by nanochannels, towards BHA. Electrochemical detection of BHA was achieved with a linear range of 0.1 µM to 5 µM and from 5 µM to 150 µM with a low limit of detection (12 nM). Owing to the fouling resistance and anti-interference capabilities of VMSF, the constructed 3D electrochemical sensor can be directly applied for the electrochemical detection of BHA in complex food samples.
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Background: Colorectal cancer is one of the top five malignant tumors in the world in terms of morbidity and mortality. Numerous long non-coding RNAs (lncRNAs) are specifically expressed in tumours and can affect various types of human cancer by participating in competitive endogenous RNA (ceRNA) regulatory networks. However, the specific mechanisms and complex networks of ceRNA regulatory patterns in colon adenocarcinoma (COAD) remain unclear. Methods: Using The Cancer Genome Atlas (TCGA) database, we identified the differentially expressed lncRNA, microRNA (miRNA), and messenger RNA (mRNA) between colon cancer and normal tissues, as well as between groups with high and low CEACAM5 expression. Then, we constructed CEACAM5-related ceRNA networks, established the key lncRNA-miRNA-mRNA regulatory axis, and explored the biological mechanisms of this axis and its clinical significance in colon cancer from multiomic aspects. Results: We constructed a ceRNA network of 18 lncRNAs, 177 miRNAs, and 25 mRNAs associated with CEACAM5 and finally established the key LCMT1-AS2/miR-454-3p/ribosomal protein S6 kinase A5 (RPS6KA5) axis associated with overall survival. Subsequent investigations have indicated that this regulatory axis could potentially participate in the progression of COAD and exert influence on the therapeutic outcomes of chemotherapy and immunotherapy. It may be involved in the PI3K-Akt signaling pathway and may modify the tumor immune microenvironment and influence the course of COAD. Additionally, it may be related to ferroptosis, N6-methyladenosine (m6A) methylation, and tumor stemness and interfere with the sensitivity of tumor cells to 5-fluorouracil and immunotherapy. Conclusions: The LCMT1-AS2/RPS6KA5 axis may be instrumental in tumor progression, potentially acting as a prognostic biomarker and therapeutic target.
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BACKGROUND: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. METHOD: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. RESULT: There was no significant difference in α diversity and ß diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. CONCLUSIONS: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Índice de Masa Corporal , ARN Ribosómico 16S/genética , Sobrepeso/complicaciones , Sobrepeso/genética , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/genética , Microambiente TumoralRESUMEN
Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.
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Neoplasias , Humanos , Linfocitos T CD8-positivos , Ciclo Celular , Membrana Celular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , PronósticoRESUMEN
The Medical Subject Headings (MeSH) is a comprehensive indexing vocabulary used to label millions of books and articles on PubMed. The MeSH annotation of a document consists of one or more descriptors, the main headings, and of qualifiers, subheadings specific to a descriptor. Currently, there are more than 34 million documents on PubMed, which are manually tagged with MeSH terms. In this paper, we describe a machine-learning procedure that, given a document and its MeSH descriptors, predicts the respective qualifiers. In our experiment, we restricted the dataset to documents with the Heart Transplantation descriptor and we only used the PubMed abstracts. We trained binary classifiers to predict qualifiers of this descriptor using logistic regression with a tfidf vectorizer and a fine-tuned DistilBERT model. We carried out a small-scale evaluation of our models with the Mortality qualifier on a test set consisting of 30 articles (15 positives and 15 negatives). This test set was then manually re-annotated by a cardiac surgeon, expert in thoracic transplantation. On this re-annotated test set, we obtained macroaveraged F1 scores of 0.81 for the logistic regression model and of 0.85 for the DistilBERT model. Both scores are higher than the macroaveraged F1 score of 0.76 from the initial PubMed manual annotation. Our procedure would be easily extensible to all the MeSH descriptors with sufficient training data and, we believe, would enable human annotators to complete the indexing work more easily.Clinical Relevance-Selecting relevant articles is important for clinicians and researchers, but also often a challenge, especially in complex subspecialties such as heart transplantation. In this study, a machine-learning model outperformed PubMed's manual annotation, which is promising for improved quality in information retrieval.
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Indización y Redacción de Resúmenes , Medical Subject Headings , Humanos , PubMed , Almacenamiento y Recuperación de la Información , Aprendizaje AutomáticoRESUMEN
The development of artificial intelligence and virtual reality technology has enabled rehabilitation service systems based on virtual scenarios to provide patients with a multi-sensory simulation experience. However, the design methods of most rehabilitation service systems rarely consider the physician-manufacturer synergy in the patient rehabilitation process, as well as the problem of inaccurate quantitative evaluation of rehabilitation efficacy. Thus, this study proposes a design method for a smart rehabilitation product service system based on virtual scenarios. This method is important for upgrading the rehabilitation service system. First, the efficacy of rehabilitation for patients is quantitatively assessed using multimodal data. Then, an optimization mechanism for virtual training scenarios based on rehabilitation efficacy and a rehabilitation plan based on a knowledge graph are established. Finally, a design framework for a full-stage service system that meets user needs and enables physician-manufacturer collaboration is developed by adopting a "cloud-end-human" architecture. This study uses virtual driving for autistic children as a case study to validate the proposed framework and method. Experimental results show that the service system based on the proposed methods can construct an optimal virtual driving system and its rehabilitation program based on the evaluation results of patients' rehabilitation efficacy at the current stage. It also provides guidance for improving rehabilitation efficacy in the subsequent stages of rehabilitation services.
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Inteligencia Artificial , Realidad Virtual , Niño , Humanos , Simulación por Computador , Interfaz Usuario-ComputadorRESUMEN
Background: Gastric cancer is one of the most common malignancies in the world and ranks fourth among cancer-related causes of death. Gastric adenocarcinoma is the most common pathological type of gastric cancer; usually, this tumor is associated with distant metastasis upon first diagnosis and has a poor prognosis. Cuproptosis is a novel mechanism of cell death induced by copper, and is closely related to tumor progression, prognosis and immune response. However, the role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of gastric cancer has yet to be elucidated. Methods: Gastric adenocarcinoma data were downloaded from the Cancer Genome Atlas (TCGA) database. Through bioinformatics analysis, a risk scoring model was constructed from cuproptosis gene-related lncRNA. Then, we investigated the relationship between prognosis and the TIME of gastric cancer according to clinical characteristics and risk score. Results: Validation of the model showed that the overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group (P < 0.001) and that the risk score was an independent predictor of prognosis (P < 0.001). The new model was significantly correlated with the prognosis and TIME of patients with gastric cancer, including immune cell infiltration, tumor mutation burden (TMB) score, targeted drug sensitivity, and immune checkpoint gene expression. In addition, a prognostic nomogram was established based on the risk score (AC008915.2, AC011005.4, AC023511.1, AC139792.1, AL355312.2, LINC01094 and LINC02476). Conclusion: Our analysis revealed that the prognostic model of cuproptosis-related genes could effectively predict the prognosis of patients with gastric cancer and comprehensively establish the relationship between cuproptosis genes and tumor immunity. This may provide a new strategy for the precise treatment of gastric cancer.
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Ferroptosis is an iron-dependent form of cell death induced by lipid oxidation with an essential role in diseases, including cancer. Since prognostic value of ferroptosis-dependent related genes (FDRGs) in colorectal cancer (CRC) remains unclear, we explored the significance of FDRGs in CRC through comprehensive single-cell analysis. We downloaded the GSE161277 dataset for single-cell analyses and calculated the ferroptosis-dependent gene score (FerrScore) for each cell type. According to each cell type-specific median FerrScore, we categorized the cells into low- and high-ferroptosis groups. By analyzing differentially-expressed genes across the two groups, we identified FDRGs. We further screened these prognosis-related genes used to develop a prognostic signature and calculated its correlation with immune infiltration. We also compared immune checkpoint gene efficacy among different risk groups, and qRT-PCR was performed in colorectal normal and cancer cell lines to explore whether the signature genes could be used as clinical prognostic indicators. In total, 523 FDRGs were identified. A prognostic signature including five signature genes was constructed, and patients were divided into two risk groups. The high-risk group had poor survival rates and displayed high levels of immune infiltration. Our newly developed ferroptosis-based prognostic signature possessed a high predictive ability for CRC.
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Neoplasias Colorrectales , Ferroptosis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Análisis de Expresión Génica de una Sola Célula/métodos , Línea Celular , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/diagnóstico , Análisis de Secuencia de ARN/métodos , PronósticoRESUMEN
PURPOSE: In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD. PATIENTS AND METHODS: Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram. RESULTS: There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82). CONCLUSIONS: The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.
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Carcinoma Hepatocelular , Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Receptor de Muerte Celular Programada 1 , Puntaje de PropensiónRESUMEN
Colorectal cancer (CRC) metastasis plays a crucial role in disease progression, yet the regulatory mechanisms underlying metastasis remain incompletely understood. Isobutyric acid (IBA), a short-chain fatty acid found at high levels in serum of CRC patients, has been shown to be a critical metabolite influencing CRC proliferation. However, its role in tumor metastasis remains unknown. Here, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, we found that levels of IBA were significantly higher in patients with distant organ metastasis of CRC than in those without. Furthermore, IBA promoted CRC metastasis both in vitro and in vivo. Mass spectrometry, immunofluorescence, and cellular thermal shift assay revealed that IBA interacts with RACK1. Mechanistically, IBA binding to and activating RACK1 promotes regulation of downstream Akt and FAK signaling and CRC metastasis. Collectively, our study highlights the critical interplay between IBA and RACK1 and its impact on tumor metastasis. This study suggests that targeting the IBA-RACK1 signaling axis may be an effective therapeutic strategy for controlling CRC metastasis.
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Neoplasias Colorrectales , Espectrometría de Masas en Tándem , Humanos , Línea Celular Tumoral , Cromatografía Liquida , Neoplasias Colorrectales/patología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Movimiento Celular , Receptores de Cinasa C Activada/metabolismo , Proteínas de Neoplasias/metabolismoRESUMEN
Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)-based anti-tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well-established Fe-metal-organic framework (Fe-MOF)-based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF-κB p65), which can boost pro-apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down-regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe-MOF-unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating-enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF-κB-related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS-based anti-tumor methods.
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Neoplasias Colorrectales , FN-kappa B , Humanos , Fosforilación , FN-kappa B/genética , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Epigénesis Genética , Ubiquitinación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genéticaRESUMEN
OBJECTIVE: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. METHOD: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. RESULT: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O - glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. CONCLUSIONS: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Interleucina-6 , Neoplasias Colorrectales/patología , Bacteroidetes/genética , Heces/microbiología , ARN Ribosómico 16S/genética , Microambiente TumoralRESUMEN
Objective: To identify differences between the composition, abundance, and biological function of the intestinal microbiome of patients with and without lymph-vascular invasion (LVI) colorectal cancer (CRC) and to construct predictive labels to support accurate assessment of LVI in CRC. Method: 134 CRC patients were included, which were divided into two groups according to the presence or absence of LVI, and their intestinal microbiomes were sequenced by 16SrRNA and analyzed for differences. The transcriptome sequencing data of 9 CRC patients were transformed into immune cells abundance matrix by CIBERSORT algorithm, and the correlation among LVI-associated differential intestinal microbiomes, immune cells, immune-related genes and LVI-associated differential GO items and KEGG pathways were analyzed. A random forest (RF) and eXtreme Gradient Boosting (XGB) model were constructed to predict the LVI of CRC patients based on the differential microbiome. Result: There was no significant difference in α-diversity and ß-diversity of intestinal microbiome between CRC patients with and without LVI (P > 0.05). Linear discriminant analysis Effect Size (LEfSe) analysis showed 34 intestinal microbiomes enriched in CRC patients of the LVI group and 5 intestinal microbiomes were significantly enriched in CRC patients of the non-lymph-vascular invasion (NLVI) group. The RF and XGB prediction models constructed with the top 15% of the LVI-associated differential intestinal microbiomes ranked by feature significance had good efficacy. Conclusions: There are 39 intestinal flora with significantly different species abundance between the LVI and NLVI groups. g:Alistipes.s:Alistipes_indistinctus is closely associated with colorectal cancer vascular invasion. LVI-associated differential intestinal flora may be involved in regulating the infiltration of immune cells in CRC and influencing the expression of immune-related genes. LVI-associated differential intestinal flora may influence the process of vascular invasion in CRC through a number of potential biological functions. RF prediction models and XGB prediction models constructed based on microbial markers of gut flora can be used to predict CRC-LVI conditions.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Biomarcadores de Tumor/análisis , Heces/químicaRESUMEN
Background: Colon cancer (CC) is the fifth most prevalent cancer around the globe and poses a major risk to human health. Even though Kremen2 serves as a prognostic indicator in individuals with malignant tumours, its role in evaluating the prognosis of individuals with colon cancer has not been confirmed. Methods: Here, we examined the protein expression of Kremen2 in CC tissues and paired adjacent normal tissues by immunohistochemistry (IHC), then analyzed the clinical and RNA-seq data presented in The Cancer Genome Atlas (TCGA) database to confirm the relationship between Kremen2 levels and CC. In addition, the associations between Kremen2 mRNA expression and infiltrating immune cells were examined. Results: The study showed that the mRNA expression and protein level of Kremen2 were increased in CC tissues compared with adjacent normal tissues. According to Kaplan-Meier analysis, high Kremen2 expression in CC was linked to poor overall survival and progression-free survival. Clinical correlation analysis highlighted that a high level of Kremen2 expression was strongly linked with tumour progression, particularly lymph node metastasis. Cox regression analysis highlighted that Kremen2 was an independent prognostic indicator for CC. Bioinformatic studies highlighted that Kremen2 might be associated with the immune status in CC. Conclusion: Increased Kremen2 could serve as a potential prognostic CC biomarker.
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Biomarcadores de Tumor , Neoplasias del Colon , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Neoplasias del Colon/patología , Metástasis Linfática , ARN MensajeroRESUMEN
Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.
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Antineoplásicos , Triterpenos , Humanos , Estructura Molecular , Triterpenos/farmacología , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Proliferación Celular , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Diseño de FármacosRESUMEN
PURPOSE: The aim of the current study was to identify the relationship between body composition changes during neoadjuvant therapy (NAT) and the treatment efficiency of NAT in gastrointestinal cancer (GC) patients. METHODS: From January 2015 to July 2020, 277 GC patients treated with NAT had included for retrospective analysis. The body mass index (BMI) and computed tomography (CT) imaging before and after NAT were recorded. The BMI change optimal cut-off value were calculated by ROC curve. Balancing essential characteristic variables using propensity score matching (PSM) method. Exploring the association between BMI changes and tumor response to NAT using logistic regression analysis. The survival outcome of matched patients between different BMI change groups was compared. RESULTS: A cutoff point of BMI change >2% during NAT was defined as BMI loss. Among the 277 patients, 110 (39.7%) patients showed BMI change with a loss after NAT. In total, 71 pairs of patients were selected for further analysis. The median follow-up time was 22 months (range 3 to 63 months). Univariate and multivariate logistic regression analyses in matched cohort showed that BMI change was a prognostic factor for tumor response after NAT in GC patients (odds ratio (OR), .471; 95% confidence interval (CI), .233-.953; P = .036). In addition, patients who experienced BMI loss after NAT showed worse overall survival than those who had BMI gain or stable. CONCLUSION: BMI loss during NAT probably may has negative effects on NAT efficiency and survival for gastrointestinal cancer patients. It is necessary to monitor and maintain weight for patients during treatment.
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Neoplasias Gastrointestinales , Terapia Neoadyuvante , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Neoplasias Gastrointestinales/tratamiento farmacológico , Pérdida de Peso , PronósticoRESUMEN
BACKGROUND: The intent of this research was to generate and investigate the D-dimer to lymphocyte ratio (DLR) capacity to forecast the risk and prognosis of colorectal cancer liver metastases (CRCLM). METHODS: From January 2010 to December 2019, 177 clinicopathologically confirmed colorectal cancer (CRC) patients (89 in the control group and 88 in the experimental group) were identified at the Affiliated Cancer Hospital of Guangxi Medical University. Multivariate Cox regression analysis was used to screen independent predictive diagnostic and prognostic factors of liver metastasis in CRC, and receiver operating characteristic (ROC) curves and KaplanâMeier (KâM) curves were established to analyze the diagnostic and predictive prognostic efficacy of the DLR in the development of CRCLM. RESULTS: Patients with CRCLM had higher DLR levels and D-dimer levels in their blood, with statistically significant differences (p < 0.001). DLR might be employed as a predictor for the development of CRCLM, according to ROC curve research (sensitivity 0.670, specificity 0.775, area under the curve 0.765). D-dimer, lymphocyte count CEA, CA125, and CA199 were not linked to prognosis in patients with CRCLM in Cox regression analysis of dichotomous variables. In contrast, DLR level was a possible risk factor for the prognosis of patients with CRCLM (HR = 2.108, p = 0.047), and age, T stage, and DLR level (DLR < 0.4) were connected with the prognosis of patients with CRCLM (p < 0.05). CONCLUSION: DLR serves as a risk indicator for the development of CRCLM.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Pronóstico , China/epidemiología , Neoplasias Hepáticas/secundario , Linfocitos/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Estudios RetrospectivosRESUMEN
Small round cell undifferentiated sarcoma is a rare and highly invasive group of malignant bone and soft tissue tumors, often associated with a high misdiagnosis rate. The patient in this case was a 34-year-old male who presented with a two-month history of abdominal pain that worsened over the past two weeks. Elevated levels of tumor markers CA19-9 and CA72-4 were observed. Imaging revealed a substantial, well-vascularized mass in the lower left abdomen, located in the posterior abdominal cavity, invading the descending colon and the root of the small mesentery, and infiltrating the serous layer. The lesion was extensively resected without any postoperative complications. Microscopic examination indicated a combination of mucinous adenocarcinoma (approximately 30%) and small round cell undifferentiated sarcoma (approximately 70%). The patient was followed up for six months, and one month after surgery, a recurrence of the tumor was observed in the left paracolonic sulcus area, with metastases to the abdominal wall, peritoneum, and medial iliac muscles. Chemotherapy and targeted therapy were administered, and the patient currently survives with the presence of tumors. Small round cell undifferentiated sarcoma is an uncommon and highly invasive tumor, and clinical surgeons need to raise their awareness and realize to the maximum extent possible that this disease can be described through a multi-modal combination of immunohistochemistry and genetic test to improve diagnostic accuracy and reduce missed diagnoses. Further research in the field of biology is necessary to explore targeted drugs specifically suitable for this disease.
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Background: The N7-methylguanosine modification (m7G) of the 5' cap structure in the mRNA plays a crucial role in gene expression. However, the relation between m7G and tumor immune remains unclear. Hence, we intended to perform a pan-cancer analysis of m7G which can help explore the underlying mechanism and contribute to predictive, preventive, and personalized medicine (PPPM / 3PM). Methods: The gene expression, genetic variation, clinical information, methylation, and digital pathological section from 33 cancer types were downloaded from the TCGA database. Immunohistochemistry (IHC) was used to validate the expression of the m7G regulator genes (m7RGs) hub-gene. The m7G score was calculated by single-sample gene-set enrichment analysis. The association of m7RGs with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. CellProfiler was used to extract pathological section characteristics. XGBoost and random forest were used to construct the m7G score prediction model. Single-cell transcriptome sequencing (scRNA-seq) was used to assess the activation state of the m7G in the tumor microenvironment. Results: The m7RGs were highly expressed in tumors and most of the m7RGs are risk factors for prognosis. Moreover, the cellular pathway enrichment analysis suggested that m7G score was closely associated with invasion, cell cycle, DNA damage, and repair. In several cancers, m7G score was significantly negatively correlated with MSI and TMB and positively correlated with TIDE, suggesting an ICB marker potential. XGBoost-based pathomics model accurately predicts m7G scores with an area under the ROC curve (AUC) of 0.97. Analysis of scRNA-seq suggests that m7G differs significantly among cells of the tumor microenvironment. IHC confirmed high expression of EIF4E in breast cancer. The m7G prognostic model can accurately assess the prognosis of tumor patients with an AUC of 0.81, which was publicly hosted at https://pan-cancer-m7g.shinyapps.io/Panca-m7g/. Conclusion: The current study explored for the first time the m7G in pan-cancer and identified m7G as an innovative marker in predicting clinical outcomes and immunotherapeutic efficacy, with the potential for deeper integration with PPPM. Combining m7G within the framework of PPPM will provide a unique opportunity for clinical intelligence and new approaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00305-1.
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Tumor cells undergo epithelial-mesenchymal transition (EMT), however, there is a room of disagreement in role of EMT heterogeneity to colorectal cancer metastasis (mCRC) evolution. To uncover new EMT-related metastasis proteins and pathways, we addressed the EMT status in colorectal cancer liver metastasis patient-derived CTCs to identify proteins that promote their distant metastasis. And then, we performed a comparative proteomic analysis in matched pairs of primary tumor tissues, adjacent mucosa tissues and liver metastatic tissues. By integrative analysis we show that, unstable Epithelial/Mesenchymal (E/M)-type CTCs had the strongest liver metastases formation ability and the proportion of E/M-type CTCs correlated with distant metastases. Using an optimized proteomic workflow including data independent acquisition (DIA) and parallel reaction monitoring (PRM), we identified novel EMT-related protein cluster (GNG2, COL6A1, COL6A2, DCN, COL6A3, LAMB2, TNXB, CAVIN1) and well-described (ERBB2) core protein level changes in EMT-related metastasis progression, and the proteomic data indicate ERBB2, COL6A1 and CAVIN1 are promising EMT-related metastatic biomarker candidates. This study contributes to our understanding of the role that EMT plays in CRC metastasis and identifies heterogeneous EMT phenotypes as a key piece for tumor progression and prognosis. We further propose that therapies targeting this aggressive subset (E/M-type) of CTCs and related protein may be worthy of exploration as potential suppressors of metastatic evolution.