Non-small cell lung cancer (NSCLC) is a serious threat to the health of older adults. Despite the significant progress in immunotherapy, effective treatments for NSCLC remain limited. The development of tumors indicates failure in immune surveillance and the successful immune escape of tumor cells. Research on the tumor immune microenvironment (TIME) revealed these opposing immune processes and contributed to the discovery of new methods to suppress the immune escape and restore the immune surveillance functions. This paper aimed to provide updates on the current findings regarding the relevance of TIME in NSCLC treatment. It also aimed to introduce the TIME, immune editing, cancer immunotherapy, and new challenges. Based on the clinical data, the combination of neoadjuvant chemotherapy and immune checkpoint inhibitor (ICI) therapy is suitable for patients with NSCLC who are not eligible to undergo surgery. Combined ICI therapy after epidermal growth factor receptor (EGFR)/tyrosine kinase inhibitor (TKI) therapy should be considered in patients with EGFR mutations. Chemoradiotherapy may increase the density of CD8 + lymphocytes, which is significantly associated with better prognosis. For older patients and those with advanced-stage disease, regional tumor treatments, such as stereotactic radiation therapy and percutaneous cryoablation, may be more suitable, but further studies are needed to confirm this. In conclusion, restoring immune surveillance is as important as removing cancerous tissues; further studies that include the use of combined treatment methods, individualized treatment plans, and immunonutrition are warranted.
Irinotecan (CPT11) is one of the most effective drugs for treating colon cancer, but its severe side effects limit its application. Recently, a traditional Chinese herbal preparation, named PHY906, has been proved to be effective for improving therapeutic effect and reducing side effects of CPT11. The aim of this study was to provide novel insight to understand the molecular mechanism underlying PHY906-CPT11 intervention of colon cancer. Based on the GSE25192 dataset, for different three treatments (PHY906, CPT11, and PHY906-CPT11), we screened out differentially expressed genes (DEGs) and constructed a co-expression network by weighted gene co-expression network analysis (WGCNA) to identify hub genes. The key genes of the three treatments were obtained by merging the DEGs and hub genes. For the PHY906-CPT11 treatment, a total of 18 key genes including Eif4e, Prr15, Anxa2, Ddx5, Tardbp, Skint5, Prss12 and Hnrnpa3, were identified. The results of functional enrichment analysis indicated that the key genes associated with PHY906-CPT11 treatment were mainly enriched in “superoxide anion generation” and “complement and coagulation cascades”. Finally, we validated the key genes by GEPIA and RT-PCR analysis, the results indicated that EIF4E, PRR15, ANXA2, HNRNPA3, NCF1, C3AR1, PFDN2, RGS10, GNG11, and TMSB4X might play an important role in the treatment of colon cancer with PHY906-CPT11. In conclusion, a total of 18 key genes were identified in this study. These genes showed strong correlation with PHY906-CPT11 treatment in colon cancer, which may help elucidate the underlying molecular mechanism of PHY906-CPT11 treatment in colon cancer.
This study was aimed to prepare a silk fibroin (SF)/chitosan (CS)/nano-Hydroxyapatite (n-HAp) composite scaffold for repair of cartilage damage. A four-layer bionic scaffold SF/CS/n-HAp was constructed by cryogenic freezing and forming. Sodium Tripolyphosphate (STPP) was used as a cross-linking agent to post-process the scaffold to improve the mechanical strength of the scaffold. The various materials prepared were characterized. The SF/CS/n-HAp scaffold prepared in this study was cream-colored cylindrical and elastic. It can show variability after external force was applied, and can be restored to its original appearance after elimination of the external force. The diameter of the scaffold was 5 cm, and the total thickness was about 1 cm. The scanning electron microscope (SEM) results showed that the surface of the scaffold material was smooth, the pore size changed gradually, and the connectivity among the holes was good. The pore size distribution of the entire scaffold material was between 100 μm∼300 μm, and the pore size range was suitable for the adhesion, expansion, and migration of chondrocytes and osteoblasts. The mechanical performance test results showed that the composite scaffold had a compression modulus of 706 kPa, which can meet the mechanical performance requirements for repair of smaller articular cartilage damage. In addition, the porosity of each layer of the scaffold was more than 91%, which was conducive to the adhesion of cells on the surface of the material. The cell experiment results revealed that the composite scaffold material was beneficial to the growth and proliferation of cells. Under osteogenic and chondrogenic induction culture, bone marrow stromal cells (BMSCs) can differentiate in the direction of osteogenesis and cartilage. The results of animal experiments revealed that the SF/CS/n-HAp material group showed better effect than the blank control group in repairing rat cartilage defects, and the Wayne score and O’Driscoll score were also significantly higher than the blank control group. This suggested that the biomimetic scaffold SF/CS/n-HAp prepared in this study showed good physical properties and biocompatibility, and had certain prospects in the application of repairing cartilage damage.
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