Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

As one of the most attention-attracting immunotherapy, immune checkpoint inhibitors (ICIs) have been approved as the first-line drugs for the therapy of various types of cancers.Nevertheless, the single application of ICIs exhibited limited efficacy, and it is easy to develop drug resistance.Therefore, the development of combination therapies become a hot topic in this field to improve the efficacy of ICIs therapy.This article describes some new ICIs targets, reveals the mechanisms of resistance, and introduces the current status of combination other therapies with ICIs therapy systematically including chemotherapy, radiotherapy, hyperthermia, antiangiogenic therapy, tumor vaccines, cytokine therapy and adoptive cellular therapy.Furthermore, the synergistic mechanism of combination therapy to enhance antitumor effect.Thus, this article provides solid references for personalized combination therapy according to the pathological characteristics of patients.

In order to evaluate the consistency of the release behavior between the self-made saxagliptin and metformin hydrochloride sustained-release tablets and the reference preparations in vitro, the similarity of the dissolution curves between the self-made preparations and the reference preparations in four dissolution mediums: HCl (pH 1.0), acetate buffer saline (pH 4.5), phosphate buffer saline (pH 6.8) and pure water, and the gel morphology and strength of the self-made preparations and the reference preparations in the HCl (pH 1.0) solution medium were compared.Results showed that in four dissolution mediums, the dissolution rates of saxagliptin in the self-made preparations and the reference preparations at 15 min were greater than 85%, and the ?2 similarity factors of metformin hydrochloride were 89, 83, 80, 86, all greater than 50, so the dissolution of the self-made preparations was consistent with those of the reference preparations.The volume expansion rate, water absorption rate and erosion rate were consistent with those of the reference preparations, and the gel strength of the self-made preparations was the same as that of the reference preparations.The in vitro release behaviors of the self-made preparations and the reference preparations are consistent, which provide a good guarantee for bioequivalence.

Pancreatic cancer stroma plays a critical role in tumor progression, invasion, metastasis and resistance.Targeting tumor cell alone could not meet the demand for prolonging patients'' survival.Growing studies have laid emphasis on developing combined regimens between targeting pancreatic cancer stroma and chemotherapy, radiotherapy and immunotherapy.We are faced with some new opportunities in spite of the great challenges brought to the research and development of targeting drugs owing to the complicated stroma components, crosstalking signal pathways and abnormal angiogenesis of pancreatic cancer.In this article, recent advances in therapeutic strategies of targeting pancreatic cancer stroma are reviewed and analyzed from the aspects of extracellular matrix (ECM), cancer associated fibroblasts (CAFs) and vessels, in the hope of providing some novel ideas for targeting therapy against pancreatic cancer.

Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in tumors, which generally exhibit anti-inflammatory M2 phenotypes, and are the key inducers of tumor development, metastasis and drug resistance, and thus becoming a popular target in the field of antitumor immunotherapy.The study and application of nanocarriers optimize TAMs-targeted antitumor therapy.According to the characteristics and functions of TAMs, modulation strategies based on TAMs are elaborated, including TAMs depletion, inhibition of TAMs recruitment and TAMs repolarization.At the same time, in order to apply the above strategies more efficiently and overcome the general off-target problems in treatment, specific TAMs-targeted therapies based on nanocarriers are reviewed and analyzed, including passive targeting to TAMs, active targeting to macrophages and specifically active targeting to M2-TAMs. Finally, based on the limitations of targeting TAMs alone, new therapeutic strategies of targeting both TAMs and tumor cells via nanocarrier based delivery systems are introduced to provide new ideas for the application of these strategies in the field of tumor immunotherapy and combination therapy with other antitumor strategies.

Solid dispersions of the insoluble compound CHMFL-KIT-110 were prepared by solvent method with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus),Poloxamer 407,PEG 6000,Copovidone (Kollidon VA64) as carriers and SLS,Tween 80,Cremophor RH40 as solubilizers. The optimal formulation was screened and obtained with dynamic solubilities and supersaturation performances as indexes. The final product was characterized by Fourier transform infrared (FT-IR),differential thermal analysis (DTA) and X-ray powder diffraction (XRPD). The stability and pharmacokinetic behavior in rats were also investigated. Results suggested that when the weight ratio of CHMFL-KIT-110/Soluplus/SLS was 1∶4∶0.5,dynamic solubility of the solid dispersions was significantly improved with no recrystallization. In the accelerated condition (40 °C,75% RH) for 30 days,CHMFL-KIT-110 in the solid dispersions was still amorphous with no crystal observed. The results of pharmacokinetics in rats showed that the cmax and AUC0→t of CHMFL-KIT-110 solid dispersions were 373.1 times and 358.7 times higher than those of free drugs,respectively. These results help to understand the formulation development and clinical practice of CHMFL-KIT-110.

Nanotechnology has brought new strategies in the area of pharmaceutical sciences, especially in the drug delivery system. Among them, the application of protein as drug carriers has drawn extensive attention. A wide variety of proteins that have been used fordrug delivery system including the common animal- and plant-basedproteins, as well as the recombinant protein nanoparticles, which possess many advantages such as biocompatibility, biodegradability, low antigenicity, higher stability and drug loading property. This system is of great significance in the fields of clinical treatment, especially targeted therapy of tumors. In this paper, the fabrication of nanoparticles from animal, botanical, and recombinant proteins are described. And then, trend of development in protein-based nanocarriers is also prospected.

Tumor-associated fibroblasts(TAFs),the most important stromal cells of the tumor microenvironment (TME),have been found to support tumorigenesis and tumor metastasis in a variety of ways,including paracrine, direct contact with cells,immune regulation and extracellular matrix remolding.Therefore,TAFs in the TME have been an optimal target for cancer therapy.In this review,the TAFs targeted therapies are summarized to provide the new strategy for tumor treatments based on the analysis of the location and specific biological phenotypes of TAFs in tumors.

Hypoxia,a salient feature of solid tumors,is often associated with invasiveness,metastasis and resistance to anticancer drugs.The strategies including the use of oxygen-carriers based on hyperbaric oxygen and blood substitutes to transport oxygen into tumors or in situ generation of O2from the tumor microenvironment endogenous H2O2have been explored to relieve the tumor hypoxia and to improve therapeutic efficiency.In addi-tion,it is potential to design hypoxia-responsive nanocarriers based on tumor hypoxia microenvironment to deliver anticancer drugs to the targeted tumor site,thereby improve drug concentrations in targeted site,significantly increase the antitumor efficiency and reduce the side-effects of drugs.This review gives an overview of the advances in relieving tumor hypoxia and hypoxia-responsive nanocarriers for tumor to provide a reference for the research and development of new antitumor drugs.