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BACKGROUND@#Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.@*METHODS@#GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis.@*RESULTS@#B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02).@*CONCLUSIONS@#B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
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Humans , Cell Line, Tumor , Neoplasm Recurrence, Local , NF-E2-Related Factor 2/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Stomach NeoplasmsABSTRACT
Background: The incidence of ulcerative colitis (UC) has gradually increased in China in recent years. The pathogenesis of UC is related to the dysfunction of immune system. B7-H5 is an important immune checkpoint molecule and is significant for the regulation of immune function. Ainis: To investigate the expression and clinical significance of B7-H5 in UC. Methods: A total of 65 UC tissue specimens were collected from Jan. 2010 to Dec. 2020 at the First Affiliated Hospital of Soochow University, and 5 healthy subjects were served as controls. Immunohistoehemistry and immunofluorescence were used to detect the expression of B7-H5, and its relationship with elinieopathologieal characteristics of UC patients was analyzed. Results: Expression of B7-H5 was significantly increased in UC patients than in controls (P 0. 05). Conclusions; The expression of B7-H5 in UC patients is significantly increased and is correlated with ESR and CRP, and can be used as a new marker for reflecting the severity of inflammation in UC patients.
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Gastrointestinal cancers are the common malignant tumors of the digestive system, and their morbidity and mortality are in the forefront of malignant tumors. Currently, cancer immunotherapy is the hottest topic in cancer research field. Although cancer immunotherapy has achieved some results in the fundamental research and clinical application of gastrointestinal tumors, there are still a series of problems that need to be resolved. In this article, we review the fundamental and clinical research progress of several common methods of cancer immunotherapy in the field of gastrointestinal tumors.
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Objective To evaluate the curative effect and safety of percutaneous argon-helium knife cryoablation in treating patients with liver metastases from gastric cancer.Methods The clinical data of 24 patients with liver metastases from gastric cancer,who had received percutaneous argon-helium knife cryoablation therapy,were retrospectively analyzed.A total of 33 metastatic lesions could be used for evaluation.CT-guided percutaneous argon-helium knife cryoablation of liver metastases was carried out in all patients.The 3-month,6-month and 12-month local control rate,overall survival (OS) rate,progression -free survival (PFS),incidence of recurrence,preoperative and postoperative quality of life,and complications were documented.Results The median follow-up time was 14 months (6-48 months).After cryoablation therapy,the quality of life was improved significantly.The 3-month,6-month and 12-mouth local control rates were 91.7％,73.9％ and 52.6％ respectively.Mter cryoablation therapy,the median PFS was 8 months (1-16 months),the median survival time was 16 months,and the one-year and 2-year survival rates were 75.0％ and 37.5％ respectively.No severe complications occurred.Conclusion For the treatment of liver metastases from gastric cancer,percutaneous argon-helium knife cuoablation is safe and effective with reliable short-term curative effect,the patient's quality of life can be well improved.