No abstract

Cyclin D1 (CCND1) amplification relevant to malignant biological behavior exists in solid tumors. The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to treatment with immune checkpoint inhibitors (ICIs) are unknown. Our study is a preliminary investigation mainly focused on the predictive function of CCND1 amplification in the tumor microenvironment (TME) in the aspect of genome and transcriptome. We examined the prevalence of CCND1 amplification and its potential as a biomarker for the efficacy of ICI therapy for solid tumors using a local database ( n = 6,536), The Cancer Genome Atlas (TCGA) database ( n = 10,606), and the Memorial Sloan Kettering Cancer Center (MSKCC) database ( n = 10,109). Comprehensive profiling was performed to determine the prevalence of CCND1 amplification and the correlation with the prognosis and the response to ICIs. A CCND1 amplification occurs in many cancer types and correlates with shorter overall survival and inferior outcomes with ICI therapy. Transcriptomic analysis showed various degrees of immune cell exclusion, including cytotoxic cells, T cells, CD8 + T cells, dendritic cells (DCs), and B cells in the TME in a TCGA CCND1 amplification population. The gene set enrichment analysis suggested that CCND1 amplification correlates with multiple aggressive, immunosuppressive hallmarks including epithelial–mesenchymal transition, transforming growth factor (TGF)-β signaling, KRAS signaling, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling, p53 pathway, and hypoxia signaling in solid tumors. These findings indicate that CCND1 amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs.

No abstract

Stratum corneum is the main obstacle for drugs to pass through the skin. Microneedles are composed of arrays of micro-projections formed with different materials, generally ranging from 25-2000 μm in height. Microneedles straightly pierce the skin with its short needle arrays to overcome this barrier. Microneedles can be divided into several categories, for instance, solid microneedles, coated microneedles, and hollow microneedles and so on. However, all these types have their weak points related to corresponding mechanisms. In recent years, pioneering scientists have been working on these issues and some possible solutions have been investigated. This article will focus on the microneedle arrays consisting of hydrogels. Hydrogels are commonly used in drug delivery field. Hydrogel microneedles can be further divided into dissolving and degradable microneedles and phase transition microneedles. The former leaves drug with matrix in the skin. The latter has the feature that drugs in the matrix are delivered while the remaining ingredients can be easily removed from the skin after usage. For drugs which are required to be used every day, the phase transition microneedles are more acceptable. This article is written in order to summarize the advantages of these designs and summarize issues to be solved which may hinder the development of this technology.