[Advances of virus-like particles as mRNA delivery vectors].

With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage.

Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity.

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens (Ag) and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. In this study, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of Ags and cytosine-guanosine oligodeoxynucleotide (CpG) to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking Ags to eTAT enhanced cytosolic delivery of the Ags.

The effect of carbon nanoparticles vs. immune colloidal gold technique test strips on parathyroid protection in total thyroidectomy: A randomized clinical trial study.

Background: The long-term effect of intraoperative usage of carbon nanoparticles (CN) and parathyroid hormone (PTH) test strip using immune colloidal gold technique (ICGT) is unclear. This study aims to compare the effect of intraoperative usage of CN and ICGT test strips on PG function.

Methods: This randomized clinical study involved adult patients who underwent total thyroidectomy.

Relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia: a systematic review and network meta-analysis.

Background: Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of available prophylactic strategies. In this study, we compared the relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia with a systematic review and network meta-analysis.

Methods: PubMed, Embase, and Cochrane Library were searched, covering the period from 1980 to May 2022, for randomized controlled trials (RCTs) comparing calcium, vitamin D 3 , activated vitamin D 3 , teriparatide, steroids, and magnesium with placebo or each other in patients receiving total or completion thyroidectomy.

Extrachromosomal DNA in HPV-Mediated Oropharyngeal Cancer Drives Diverse Oncogene Transcription.

Purpose: Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood.

Experimental Design: Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC).

Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo.

Protein delivery with cell-penetrating peptide is opening up the possibility of using targets inside cells for therapeutic or biological applications; however, cell-penetrating peptide-mediated protein delivery commonly suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting in vivo efficacy. Here, we present an intracellular protein delivery system consisting of four modules in series: cell-penetrating peptide, pH-dependent membrane active peptide, endosome-specific protease sites and a leucine zipper. This system exhibits enhanced delivery efficiency and serum tolerance, depending on proteolytic cleavage-facilitated endosomal escape and leucine zipper-based dimerisation.

Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma.

Several comprehensive studies have demonstrated that the NOTCH pathway is altered in a bimodal manner in head and neck squamous cell carcinoma (HNSCC). In a previous study, it was found that the NOTCH4/HEY1 pathway was specifically upregulated in HNSCC and promoted epithelial‑mesenchymal transition (EMT), and that HEY1 activation supported SOX2 expression. However, the interactions in this pathway have not yet been fully elucidated.

Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks.

Precise gene editing is-or will soon be-in clinical use for several diseases, and more applications are under development. The programmable nuclease Cas9, directed by a single-guide RNA (sgRNA), can introduce double-strand breaks (DSBs) in target sites of genomic DNA, which constitutes the initial step of gene editing using this novel technology. In mammals, two pathways dominate the repair of the DSBs-nonhomologous end joining (NHEJ) and homology-directed repair (HDR)-and the outcome of gene editing mainly depends on the choice between these two repair pathways.

HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.

The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome.

Aberrant expression of CPSF1 promotes head and neck squamous cell carcinoma via regulating alternative splicing.

Alternative mRNA splicing increases protein diversity, and alternative splicing events (ASEs) drive oncogenesis in multiple tumor types. However, the driving alterations that underlie the broad dysregulation of ASEs are incompletely defined. Using head and neck squamous cell carcinoma (HNSCC) as a model, we hypothesized that the genomic alteration of genes associated with the spliceosome may broadly induce ASEs across a broad range of target genes, driving an oncogenic phenotype.

Targeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV-Positive Oropharyngeal Cancer.

Objective: The incidence and survivorship of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) are increasing. Presence of HPV DNA and epigenetic alterations in salivary rinses are independently associated with clinical prognosis. We evaluated the utility of a combined panel in detecting disease recurrence during surveillance.

Cannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation.

Purpose: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is associated with daily marijuana use and is also increasing in parallel with increased marijuana use in the United States. Our study is designed to define the interaction between cannabinoids and HPV-positive HNSCC.

Experimental Design: The expression of cannabinoid receptors and was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data.

Rational genomic optimization of DNA detection for human papillomavirus type 16 in head and neck squamous cell carcinoma.

Background: We aimed to use genomic data for optimizing polymerase chain reaction (PCR) primer/probe sets for detection of human papillomavirus (HPV)-16 in body fluids of patients with HPV-related head and neck squamous cell carcinoma (HPV-HNSCC).

Methods: We used genomic HPV-HNSCC sequencing data from a single institutional and a TCGA cohort. Optimized primer/probe sets were designed and tested for analytical performance in CaSki HPV-16 genome and confirmed in salivary rinse samples from patients with HPV-HNSCC.

miR-30e-5p represses angiogenesis and metastasis by directly targeting AEG-1 in squamous cell carcinoma of the head and neck.

Metastasis is a critical determinant for the treatment strategy and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). However, the mechanisms underlying SCCHN metastasis are poorly understood. Our study sought to determine the key microRNA and their functional mechanisms involved in SCCHN metastasis.

A novel splice variant of LOXL2 promotes progression of human papillomavirus-negative head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently diagnosed cancers worldwide. LOXL2 demonstrates alternative splicing events in patients with human papillomavirus (HPV)-negative HNSCC. The current study explored the role of a dominant LOXL2 variant in HPV-negative HNSCC.

Publisher Correction: Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.

The original version of this Article contained an error in the author affiliations. Trey Ideker was incorrectly associated with 'Department of Medicine (Oncology), Stanford University School of Medicine, 875 Blake Wilbur Dr, Palo Alto, CA 94304, USA.' This has now been corrected in both the PDF and HTML versions of the Article.

Wnt3a promotes radioresistance via autophagy in squamous cell carcinoma of the head and neck.

The canonical Wnt/β-catenin signalling pathway and autophagy play critical roles in cancer progression. However, the role of Wnt-mediated autophagy in cancer radioresistance remains unclear. In this study, we found that irradiation activated the Wnt/β-catenin and autophagic signalling pathways in squamous cell carcinoma of the head and neck (SCCHN).

Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.

Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing.

Mutation of chromatin regulators and focal hotspot alterations characterize human papillomavirus-positive oropharyngeal squamous cell carcinoma.

Background: Human papillomavirus (HPV)-associated oropharyngeal cancer is a disease clinically and biologically distinct from smoking-related head and neck squamous cell carcinoma (HNSCC). Despite its rapidly increasing incidence, the mutational landscape of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) remains understudied.

Methods: This article presents the first mutational analysis of the 46 HPV+ OPSCC tumors within the newly expanded cohort of 530 HNSCC tumors from The Cancer Genome Atlas.

Variations in HPV function are associated with survival in squamous cell carcinoma.

Incidence of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has been increasing dramatically. Although long-term survival rates for these patients are high, they often suffer from permanent radiotherapy-related morbidity. This has prompted the development of de-escalation clinical protocols to reduce morbidity.

Discovery and development of differentially methylated regions in human papillomavirus-related oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) exhibits a different composition of epigenetic alterations. In this study, we identified differentially methylated regions (DMRs) with potential utility in screening for HPV-positive OPSCC. Genome wide DNA methylation was measured using methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) in 50 HPV-positive OPSCC tissues and 25 normal tissues.

Characterization of Alternative Splicing Events in HPV-Negative Head and Neck Squamous Cell Carcinoma Identifies an Oncogenic DOCK5 Variant.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, and alternative splicing is considered to play important roles in tumor progression. Our study is designed to identify alternative splicing events (ASEs) in human papillomavirus (HPV)-negative HNSCC. RNA sequencing data of 407 HPV-negative HNSCC and 38 normal samples were obtained from The Cancer Genome Atlas (TCGA), and splice junctions were discovered using MapSplice.

The - Pathway Induces Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma.

Recently, several comprehensive genomic analyses demonstrated and mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the pathway is closely related to HNSCC progression. However, the role of in HNSCC is less well understood.

Autophagy inhibition impairs the epithelial-mesenchymal transition and enhances cisplatin sensitivity in nasopharyngeal carcinoma.

Drug resistance restricts the efficacy of cisplatin in the treatment of nasopharyngeal carcinoma (NPC). Increasing evidence indicates that autophagy and the epithelial-mesenchymal transition (EMT) participate in cancer progression and drug sensitivity. The aim of the present study was to investigate the function of autophagy and EMT in cisplatin treatment, and to reveal the underlying impact of autophagy on the EMT process in NPC.

miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by targeting WNT2B .

MicroRNAs (miRs) have been recognised as important regulators of malignant behaviour in different types of human cancer, including nasopharyngeal carcinoma (NPC). A previous study by our group revealed that miR-185-3p regulates the radioresistance of NPC cells. The present study aimed to investigate the effect of miR-185-3p on NPC invasion and metastasis.