c-Met is a chimeric antigen receptor T-cell target for treating recurrent nasopharyngeal carcinoma.

BACKGROUND AIMS: Radiation therapy is the standard treatment for patients with nasopharyngeal carcinoma (NPC), but relapse occurs in 10% to 20% of patients. The treatment of recurrent nasopharyngeal carcinoma (rNPC) remains challenging. Chimeric antigen receptors (CAR)-T-cell therapy has achieved good outcomes in the treatment of leukemia and seems to be a promising therapeutic strategy for solid tumors. c-Met has been found to be highly expressed in multiple cancer types, and the activation of c-Met leads to the proliferation and metastasis of cancer cells. However, the expression of c-Met in rNPC tissues and whether it can be used as a target for CAR-T therapy in rNPC remain to be investigated. METHODS: We detected the expression of c-Met in 24 primary human rNPC tissues and three NPC cell lines and constructed two different antibody-derived anti-c-Met CARs, namely, Ab928z and Ab1028z. To estimate the function of these two different c-Met-targeted CAR-T cells, CD69 expression, cytotoxicity and cytokine secretion of CAR-T cells were assessed after coculture with target cells. A cell line-derived xenograft mouse model also was used to evaluate these two anti-c-Met CAR-T cells. Furthermore, we determined whether combination with an anti-EGFR antibody could promote the antitumor effect of CAR-T cells in a patient-derived xenograft mouse model. RESULTS: High c-Met expression was detected in 23 of 24 primary human rNPC tissues by immunohistochemistry staining and in three NPC cell lines by flow cytometry. Ab928z-T cells and Ab1028z-T cells showed significantly upregulated expression of CD69 after coculture with targeted cells. However, Ab1028z-T cells showed superior cytokine secretion and antitumor activity. Furthermore, Ab1028z-T cells effectively suppressed tumor growth compared with control CAR-T cells, and the combination with nimotuzumab further enhanced the tumor-clearing ability of Ab1028z-T cells. CONCLUSIONS: We found that c-Met is highly expressed in rNPC tissues and confirmed its potential as a CAR-T target for rNPC. Our study provides a new idea for the clinical treatment of rNPC.

CD44 Drives M1 Macrophage Polarization in Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy is a typical complication of diabetes, which can facilitate the risk of blindness in severe cases. We sought to determine the function of CD44 in inflammatory responses of human retinal microvascular endothelial cells (HRMECs) and macrophage polarization during diabetic retinopathy (DR). METHODS: The hub genes were tested based on two datasets from the Gene Expression Omnibus database. Gene Ontology and pathway enrichment analysis was conducted on the base of differentially expressed genes (DEGs). The infiltration score and infiltration of the immune cells were assessed, and the link between key genes and macrophages was analyzed. The role of CD44 in HRMECs and macrophage polarization was determined by quantitative reverse transcription polymerase chain reaction, western blot, cell counting kit-8, Enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence. RESULTS: DEGs were enriched in several pathways linked to DR, such as cellular response to retinoic acid, retinol metabolic process, retina homeostasis, PI3K-AKT signaling pathway, and leukocyte transendothelial migration. A total of 144 DEGs were identified by up-regulation both in GSE102485 and GSE160306. Moreover, the infiltration of macrophages was greater in the DR group than that in the control group. We highlighted an obvious increase in the expression of CD44 and CD86 in patients with DR, and distinct positive associations were found between levels of macrophages and levels of CD44 and CD86. Furthermore, CD44 expression was substantially increased in HRMECs under high glucose (HG) conditions and CD44 knockdown markedly inhibited HG-induced inflammatory responses of HRMECs. HG-induced HRMECs remarkably influenced M1 polarization of macrophages, but CD44 knockdown significantly nullified this effect. CONCLUSIONS: CD44 influenced the advancement of DR via meditating M1 polarization of macrophages. Our findings could enhance the understanding of the mechanism of DR, which might offer a therapeutic target for DR patients.

Effects of Swallowing Rehabilitation Training with a Balloon Dilation Therapy on the Deglutition Function and Quality of Life of Patients with Dysphagia after Radiotherapy for Nasopharyngeal Carcinoma.

Objective: The aim of this study is to investigate the effects of swallowing rehabilitation training with a balloon dilation therapy on the deglutition function and quality of life of patients with dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The study was a retrospective study. The data of the 100 patients with dysphagia after NPC radiotherapy in our hospital between April 2021 and April 2022 were retrospectively analyzed. The patients were separated into the control group (n = 50) and experimental group (n = 50) according to their different treatments that were balloon dilation for the former and balloon dilation with swallowing rehabilitation training for the latter. The deglutition function, which was comprehensively evaluated by Kubota's water swallow test and assessments of penetration/aspiration and pharyngeal residue, and quality of life were compared between the two groups. Results: The scores of Kubota's water swallow test, penetration aspiration scale (PAS), and Yale pharyngeal residue severity rating scale (YPR-SRS) in the experimental group after treatment were (2.04 ± 0.66), (2.92 ± 1.07), and (2.42 ± 0.90), respectively, which were remarkably lower than (2.58 ± 0.78), (4.38 ± 1.51), and (2.78 ± 0.86) in the control group, with distinct differences in the data between both the groups (P < 0.05). The quality of life of patients in the experimental group was distinctly better than that in the control group (P < 0.001). Conclusion: Swallowing rehabilitation training in combination with a balloon dilation therapy can improve the deglutition function in patients with dysphagia after NPC radiotherapy as well as their quality of life, with a clinical application value.

CDR1as is overexpressed in laryngeal squamous cell carcinoma to promote the tumour's progression via miR-7 signals.

OBJECTIVES: To investigate the roles played by the circular RNA (circRNA) molecule ciRS-7 (CDR1as) and tumour suppressor miRNA-7 (miR-7) in laryngeal squamous cell carcinoma (LSCC). METHODS: Specimens of LSCC tissue (n = 30) and corresponding relative normal tissue (n = 30) were collected to determine their levels and clinical significance of CDR1as/mir-7 expression. The CDR1as and miR-7 were overexpressed in LSCC cells to investigate its function and mechanism in vitro and in vivo. RESULTS: Patients with high TNM stages, poorly differentiated tumours, lymph node metastases and poor prognosis had high CDR1as levels but low miR-7 levels. CDR1 expression was negatively associated with miR-7 expression in LSCC. Overexpression of CDR1as in vitro enhanced cell vitality, and promoted the proliferation, migration, and invasion of two LSCC cell lines (Hep2 and AMC-HN-8.) However, these effects could be abrogated by knockdown of CDR1as or the forced expression of miR-7. Mechanistically, overexpressed CDR1 molecules functioned as miR-7 sponges and upregulated the key targets of miR-7, CCNE1, and PIK3CD in Hep2 and AMC-HN-8 cells. In vivo studies demonstrated the tumourigenic role of CDR1as. Overexpression of CDR1as alone promoted tumour growth and increased expression of the proliferation indices ki-67, CCNE1, and PIK3CD. Although the tumour suppressor miR-7 effectively inhibited the tumour growth, this effect could be counteracted by co-treatment with CDR1as in vivo. CONCLUSION: CDR1as is an oncogene that promotes LSCC progression by regulating miR-7 signals.