Intratumor heterogeneity significantly challenges the accuracy of existing prognostic models for esophageal squamous cell carcinoma (ESCC) by introducing biases related to the varied genetic and molecular landscapes within tumors. Traditional models, relying on single-sample, single-region bulk RNA sequencing, fall short of capturing the complexity of intratumor heterogeneity. To fill this gap, we developed a computational model for intratumor heterogeneity corrected signature (ITHCS) by employing both multiregion bulk and single-cell RNA sequencing to pinpoint genes that exhibit consistent expression patterns across different tumor regions but vary significantly among patients.
View Article and Find Full Text PDFThe emergence of antimicrobial-resistant bacterial infections poses a significant threat to public health, necessitating the development of innovative and effective alternatives to antibiotics. Photodynamic therapy (PDT) and immunotherapy show promise in combating bacteria. However, PDT's effectiveness is hindered by its low specificity to bacteria, while immunotherapy struggles to eliminate bacteria in immunosuppressive environments.
View Article and Find Full Text PDFRespiratory diseases are highly prevalent in the general population, and the morbidity, mortality, and healthcare burden on society at large have been on the rise worldwide. For example, lung cancer is a major contributor to cancer-related mortality around the globe, and identifying clinically relevant biomarkers for lung cancer detection at both early and metastatic stages has been a pressing need. Human metabolism is complicated and may vary with different individuals.
View Article and Find Full Text PDFIn "immune-cold" tumors, the upregulation of immunosuppressive cells and insufficient infiltration of lymphocytes contribute to the resistance against immune therapy. Herein, we have developed a dual-enzyme-like photosensitive nanozyme (PBAF) to remodel the tumor immunosuppressive microenvironment (TIME) and induce the tumor infiltration of cytotoxic T lymphocytes (CTLs). Specifically, PBAF exhibits peroxidase (POD)-like activity and glutathione oxidase (GSHOx)-like activity and can be stimulated by 750 nm laser, promoting oxidative stress at the tumor site.
View Article and Find Full Text PDFBackground: Many studies have demonstrated the relationship between METTL3 protein expression and clinical outcomes in various cancers and elucidated the mechanism by which METTL3 disrupts the behavior of cancer cells. Here, we attempted to define the prognostic value of METTL3 protein in patients with cancer via systematic analysis and explored the potential effect of inhibiting METTL3 using its specific inhibitor.
Methods: We searched PubMed, Embase, and the Web of Science databases for studies that elucidated the prognostic value of METTL3 protein expression in all cancer types and then calculated the pooled hazard ratios with 95% confidence intervals for the overall survival (OS) of all cancer types and subgroups.
Objective: Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking.
View Article and Find Full Text PDFBackground: METTL3 plays a significant role as a catalytic enzyme in mediating N6-methyladenosine (mA) modification, and its importance in tumour progression has been extensively studied in recent years. However, the precise involvement of METTL3 in the regulation of translation in non-small cell lung cancer (NSCLC) remains unclear.
Results: Here we discovered by clinical investigation that METTL3 expression is correlated with NSCLC metastasis.
Background: Comprehensive analysis of transcriptomic profiles of non-small cell lung cancer (NSCLC) may provide novel evidence for biomarkers associated with response to PD-1/PD-L1 immune checkpoint blockade (ICB).
Methods: We utilized weighted gene co-expression network analysis (WGCNA) to analyze transcriptomic data from two NSCLC datasets from Gene Expression Omnibus (GSE135222 and GSE126044) that involved patients received ICB treatment. We evaluated the correlation of co-expression modules with ICB responsiveness and functionally annotated ICB-related modules using pathway enrichment analysis, single-cell RNA sequencing, flow cytometry and alternative splicing analysis.
In non-small cell lung cancer (NSCLC), the heterogeneity promotes drug resistance, and the restricted expression of programmed death-ligand 1 (PD-L1) limits the immunotherapy benefits. Based on the mechanisms related to translation regulation and the association with PD-L1 of methyltransferase-like 3 (METTL3), the novel small-molecule inhibitor STM2457 is assumed to be useful for the treatment of NSCLC. We evaluated the efficacy of STM2457 in vivo and in vitro and confirmed the effects of its inhibition on disease progression.
View Article and Find Full Text PDFIn a previous study, our research group observed that estrogen promotes the metastasis of non-small cell lung cancer (NSCLC) through the estrogen receptor β (ERβ). Invadopodia are key structures involved in tumor metastasis. However, it is unclear whether ERβ is involved in the promotion of NSCLC metastasis through invadopodia.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
April 2023
Esophageal cancer is one of the major life-threatening diseases in the world. RNA methylation is the most common post-transcriptional modification and a wide-ranging regulatory system controlling gene expression. Numerous studies have revealed that dysregulation of RNA methylation is critical for cancer development and progression.
View Article and Find Full Text PDFMetastases contribute to the low survival rate of non-small cell lung cancer (NSCLC) patients. Targeting lipid metabolism for anticancer therapies is attractive. Accumulative evidence shows that stearoyl-CoA desaturases1 (SCD1), a key enzyme in lipid metabolism, enables tumor metastasis and the underlying mechanism remains unknown.
View Article and Find Full Text PDFBackground: Centromere proteins (CENPs) form a large protein family. Sixteen proteins in this family are positioned at the centromere throughout the cell cycle. The overexpression of CENPs is common in many cancers and predicts a poor prognosis.
View Article and Find Full Text PDFAberrant translation, a characteristic feature of cancer, is regulated by the complex and sophisticated RNA binding proteins (RBPs) in the canonical translation machinery. N6-methyladenosine (mA) modifications are the most abundant internal modifications in mRNAs mediated by methyltransferase-like 3 (METTL3). METTL3 is commonly aberrantly expressed in different tumors and affects the mRNA translation of many oncogenes or dysregulated tumor suppressor genes in a variety of ways.
View Article and Find Full Text PDFEsophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment.
View Article and Find Full Text PDFThe successful treatment of breast cancer is hampered by toxicity to normal cells, impaired drug accumulation at the tumor site, and multidrug resistance. We designed a novel multifunctional liposome, CUR-DTX-L, to co-deliver curcumin (CUR) and the chemotherapeutic drug docetaxel (DTX) for the treatment of breast cancer in order to address multidrug resistance (MDR) and the low efficacy of chemotherapy. The mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of CUR-DTX-L were 208.
View Article and Find Full Text PDFBackground: Bone morphogenetic proteins (BMPs) regulate tumor progression binding to their receptors (BMPRs). However, the expression and clinical significance of BMPs/BMPRs in lung adenocarcinoma remain unclear due to a lack of systematic studies.
Methods: This study screened differentially expressed BMPs/BMPRs (deBMPs/BMPRs) in a training dataset combining TCGA-LUAD and GTEx-LUNG and verified them in four GEO datasets.
Background: An increasing number of original studies suggest that estrogen receptor beta (ERβ) expression may be related to non-small cell lung cancer (NSCLC) prognosis; however, the evidence remains inconclusive and conflicting. We aimed to systematically evaluate the expression and prognostic value of ERβ in NSCLC, and to explain the inconsistency between ERβ protein and mRNA level.
Methods: PubMed, Embase, and Web of Science databases were searched for studies (published before October 6, 2020) reporting the prognostic value of ERβ protein expression in NSCLC.
Although electroacupuncture (EA) has become a worldwide practice, little is understood about its precise target in the central nervous system (CNS) and the cell type-specific analgesia mechanism. In the present study, we found that EA has significant antinociceptive effects both in inflammatory and neuropathic pain models. Chemogenetic inhibition of GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG) replicated the effects of EA, whereas the combination of chemogenetic activation of GABAergic neurons and chemogenetic inhibition of glutamatergic neurons in the vlPAG was needed to reverse the effects of EA.
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