Background: Exosomes play an important role in information transfer among different cell types, as they transport materials from the cell membrane to the cytoplasm. They are involved not only in normal physiological functions, but also in the occurrence and development of a variety of diseases. Cancer is a major health problem affecting humans. Currently, exosomes are considered novel stars in tumor therapy. Objective: To present a review focusing on the role of exosomes in tumorigenesis and development and the possibility of treating tumors with exosome-targeted therapies or using exosomes as carriers. Methods: We reviewed literature related to the biological origin and function of exosomes and exosome-tumor relationship. Results: Exosomes are closely related to tumor immunity, angiogenesis, pre-metastasis microenvironment, chemoresistance, energy metabolism, etc. Tumor therapy involving the targeting of exosomes involves block the generation, secretion, uptake of exosomes, and elimination of circulating exosomes, and develop antitumor vaccines. Exosome as delivery vehicles can loaded with chemotherapeutic drugs, therapeutic genes, and other therapeutic drugs to target cells. Prospects and challenges of exosome-based tumor therapy are also discussed. Conclusion: Exosomes are involved in multiple processes during tumor development and should be further studied as novel targets for cancer therapy.

There is a significant correlation between the degree of tumor differentiation and the survival of patients with gastric cancers. In this report, we compared proteomic differences between poorly differentiated gastric adenocarcinoma tissues and welldifferentiated gastric adenocarcinoma tissues in order to identify differentiation-related proteins that may be closely correlated with differentiation of gastric cancer pathogenesis. We identified 7 proteins, of which calreticulin precursor, tapasinERP57 heterodimer, pyruvate kinase isozymes M1/M2 isoform M2, class Pi glutathione S-transferase, and chain A crystal structure of human enolase 1 were upregulated in poorly differentiated gastric adenocarcinoma compared with well-differentiated gastric adenocarcinoma, while myosin-11 isoform SM2A and actin alpha cardiac were downregulated. Two of them, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 are enzymes involved in glycolytic pathway. The upregulation of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 in poorly differentiated gastric adenocarcinoma was confirmed by Western blotting and immunohistochemistry. Furthermore, we observed 107 cases with gastric adenocarcinoma and found that the high expression of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 correlates with tumor size (P ¼ .0001 and P ¼ .0017, respectively), depth of invasion (P ¼ .0024 and P ¼ .0261, respectively), and poor prognosis of patients. In conclusion, with this proteomic analysis, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 were identified upregulated in poorly differentiated gastric adenocarcinoma comparing with well-differentiated gastric adenocarcinoma. The expression level of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 was significantly correlated with overall survival. Some of them would be differentiation-related cancer biomarkers and are associated with tumor metastasis, invasion, and prognosis.

Increasing the immunogenicity of tumors is considered to be an effective means to improve the synergistic immune effect of radiotherapy. Carbon ions have become ideal radiation for combined immunotherapy due to their particular radiobiological advantages. However, the difference in time and dose of immunogenic changes induced by Carbon ions and X-rays has not yet been fully clarified. To further explore the immunogenicity differences between carbon ions and X-rays induced by radiation in different “time windows” and “dose windows.” In this study, we used principal component analysis (PCA) to screen out the marker genes from the single-cell RNA-sequencing (scRNA-seq) of CD8+ T cells and constructed a protein-protein interaction (PPI) network. Also, ELISA was used to test the exposure levels of HMGB1, IL-10, and TGF-β under different “time windows” and “dose windows” of irradiation with X-rays and carbon ions for A549, H520, and Lewis Lung Carcinoma (LLC) cell lines. The results demonstrated that different marker genes were involved in different processes of immune effect. HMGB1 was significantly enriched in the activated state, while the immunosuppressive factors TGF-β and IL-10 were mainly enriched in the non-functional state. Both X-rays and Carbon ions promoted the exposure of HMGB1, IL-10, and TGF-β in a time-dependent manner. X-rays but not Carbon ions increased the HMGB1 exposure level in a dose-dependent manner. Besides, compared with X-rays, carbon ions increased the exposure of HMGB1 while relatively reduced the exposure levels of immunosuppressive factors IL-10 and TGF-β. Therefore, we speculate that Carbon ions may be more advantageous than conventional X-rays in inducing immune effects.

Abstract.Helicobacter pylori (H. pylori) infection plays an important role in the development of gastric carcinomas. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel human oncoprotein that functions as an important regulator of cell growth and malignant transformation. In the present study, we aimed to investigate the potential mechanisms by which H. pylori upregulates the expression of CIP2A and the functional impact of H. pylori-induced CIP2A in gastric cancer cells. We demonstrated that infection of MKN-45 cells with H. pylori led to a marked increase in the expression of CIP2A at the mRNA and protein levels. H. pylori-induced CIP2A was associated with increased cell proliferation. In addition, H. pylori was found to activate the JNK2 pathway. Importantly, both H. pylori-induced CIP2A production and cell proliferation were partially reversed by inhibition of JNK2 signaling. Similarly, the blockade of H. pylori-induced CIP2A expression by siRNA against CIP2A also inhibited cell proliferation. Thus, H. pylori appears to stimulate the expression of CIP2A and proliferation of gastric cancer cells via JNK2 signaling. These findings suggest that H. pylori-induced upregulation of CIP2A contributes to the development and progression of gastric cancer. Further in vivo studies are warranted to explore the biological role of CIP2A and its interaction with JNK2 signaling in gastric cancer.

No abstract