Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021.

Background: Chimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field. Methods: Literature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software. Results: A total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing. Conclusion: CAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.

Correction: Antegrade versus retrograde facial nerve dissection in benign parotid surgery: Is there a difference in postoperative outcomes? A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0206028.].

Antegrade versus retrograde facial nerve dissection in benign parotid surgery: Is there a difference in postoperative outcomes? A meta-analysis.

OBJECTIVE: The primary aim of this meta-analysis was to test the null hypothesis of no difference in facial nerve dysfunction in studies that compared classical antegrade facial nerve dissection (AFND) versus retrograde facial nerve dissection (RFND) during benign parotid surgery. METHODS: A comprehensive search of PubMed, the Cochrane Central Register of Controlled Trials, Scopus, Google Scholar, Science Direct and relevant journals was undertaken up to June 27, 2018. Randomized controlled clinical trials (RCTs), controlled clinical trials (CCTs), and retrospective studies aimed at comparing the effect of AFND vs. RFND during parotidectomy were included. The outcome measures included facial nerve dysfunction, Frey's syndrome, recurrence, silaocele, salivary fistula, operating time length of hospital stay, and estimated blood loss. Pooled risk ratio (RR) and weighted mean differences (MD) with 95% confidence intervals were calculated using either a fixed-effects or random-effects model. RESULTS: Ten studies; four RCTs and five retrospective studies were included. There were 570 patients (319 in RFND group and 251 in AFND group). 481 patients in 9 studies reported the incidence rate of facial nerve dysfunction. No statistical significant difference was observed between both groups concerning the occurrence of transient or permanent facial nerve paralysis (p = 0.44 and 0.11 respectively). One out 10 studies reported the incidence rate of sialocele, however no statistical difference was observed between the two techniques. There was reduction in the operative time (19.30 min), amount of blood loss (25.08 ml) and amount of healthy salivary tissues removed (12.20 mm) in RFND compared with AFND. CONCLUSIONS: According to the results of the current review there is no evidence demonstrating a significant advantage of one approach over another, therefore, well-designed standardized RCTs are required.

Mesenchymal stem cell-derived CCN2 promotes the proliferation, migration and invasion of human tongue squamous cell carcinoma cells.

Recent studies have demonstrated that mesenchymal stem cells (MSC) exhibit a tropism to tumors and form the tumor stroma. In addition, we found that MSC can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSC that were co-cultured with TSCC cells. To evaluate the relationship between CCN2 and TSCC growth, we downregulated MSC-derived CCN2 expression with shRNA targeting CCN2 and found that MSC-secreted CCN2 promotes TSCC cell proliferation, migration and invasion. We also confirmed that MSC-derived CCN2 partially accelerated tumor growth in vitro. Taken together, these results suggest that MSC-derived CCN2 contributes to the promotion of proliferation, migration and invasion of TSCC cells and may be a possible therapy target in the future.

PDGF-D/PDGFRß promotes tongue squamous carcinoma cell (TSCC) progression via activating p38/AKT/ERK/EMT signal pathway.

Platelet-derived growth factor D (PDGF-D) signaling plays significant roles during the development and progression of human malignancies via interacting with the receptor of PDGF-D (PDGFR). Meanwhile, the majority of human tumor metastasis is closely associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanism between PDGF-D/PDGFR signaling and EMT which involved in tumor metastasis remain dismal. This study aimed to investigate the role of PDGF-D signaling during EMT process of tongue squamous cell carcinoma (TSCC). In our study, the expression of PDGF-D and PDGFR were examined in primary TSCC samples and the expression of PDGF-D was also determined in TSCC cell lines. In addition, the correlation between PDGF-D expression and TSCC aggressive histopathological features was analyzed. Our results implied that upregulation of PDGFRß in UM1 cells induced with exogenous PDGF-D can remarkably promote tumor cells invasiveness; conversely, when using small interfering RNA (siRNA), the invasiveness can be severely prohibited. Furthermore, PDGF-D downstream signal molecules p38, AKT, ERK and EMT biomarkers (E-cadherin, N-cadherin, Vimentin and snail) were measured using Western blot. Our results showed that PDGF-D can induce p38, AKT and ERK phosphorylation; downregulate epithelial markers and upregulate mesenchymal markers. On the contrary, PDGFRß siRNA significantly prohibited p38, AKT and ERK phosphorylation; inhibited EMT process. Function analysis revealed that PDGFRß siRNA obviously interfered with UM1 cell migration and invasion, according to transwell and wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the PDGF-D/PDGFRß axis in TSCC, and then involved in the tumor cell invasion via activation of p38/AKT/ERK/EMT pathway.