Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology.

CAR-T cell therapy, a novel immunotherapy, has made significant breakthroughs in clinical practice, particularly in treating B-cell-associated leukemia and lymphoma. However, it still faces challenges such as poor persistence, limited proliferation capacity, high manufacturing costs, and suboptimal efficacy. CRISPR/Cas system, an efficient and simple method for precise gene editing, offers new possibilities for optimizing CAR-T cells. It can increase the function of CAR-T cells and reduce manufacturing costs. The combination of CRISPR/Cas9 technology and CAR-T cell therapy may promote the development of this therapy and provide more effective and personalized treatment for cancer patients. Meanwhile, the safety issues surrounding the application of this technology in CAR-T cells require further research and evaluation. Future research should focus on improving the accuracy and safety of CRISPR/Cas9 technology to facilitate the better development and application of CAR-T cell therapy. This review focuses on the application of CRISPR/Cas9 technology in CAR-T cell therapy, including eliminating the inhibitory effect of immune checkpoints, enhancing the ability of CAR-T cells to resist exhaustion, assisting in the construction of universal CAR-T cells, reducing the manufacturing costs of CAR-T cells, and the security problems faced. The objective is to show the revolutionary role of CRISPR/Cas9 technology in CAR-T cell therapy for researchers.

MiR-129-5p Restrains Apatinib Resistance in Human Gastric Cancer Cells Via Downregulating HOXC10.

Background: Repeated administration of apatinib has resulted in serious drug resistance in gastric cancer (GC). Previous studies showed that miR-129-5p had a low expression in GC, and homeobox gene C10 (HOXC10), a carcinogenic gene, was highly expressed in GC, while the molecular mechanism of miR-129-5p involved in apatinib resistance in GC cells is still unclear. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-129-5p and HOXC10 in GC tissues or cell lines. The expression levels of associated proteins were detected by Western blot. Cell counting kit-8 (CCK-8), the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and flow cytometry assays were conducted to detect cell viability, proliferation, and apoptosis of MGC-803/AP and AGS/AP cells in vitro. The dual-luciferase reporter assay was used to verify the targeted relationship between miR-129-5p and HOXC10. The xenograft model was established to examine the effect of miR-129-5p in vivo, and the HOXC10 protein expression in tumor xenograft was assessed by immunohistochemistry. Results: MiR-129-5p had a low expression in GC tissues and apatinib-resistant cell lines, while HOXC10 was highly expressed. Meanwhile, overexpression of miR-129-5p and knockdown of HOXC10 could enhance the chemosensitivity of MGC-803/AP and AGS/AP cells. Dual-luciferase reporter assay confirmed miR-129-5p targeted HOXC10 and downregulated its expression level. MiR-129-5p inhibited proliferation and promoted apoptosis of MGC-803/AP and AGS/AP cells by downregulating HOXC10. The experiment in vivo also confirmed that miR-129-5p reduced apatinib resistance in GC cells by targetedly inhibiting HOXC10. HOXC10 was upregulated in GC tumor xenograft tissues. Conclusion: miR-129-5p restrains apatinib-resistant of GC cells by regulating HOXC10.

A propensity score-matched comparison of laparoscopic distal versus total gastrectomy for middle-third advanced gastric cancer.

BACKGROUND: The optimal resection extent for middle-third advanced gastric cancer (AGC) still remains controversial. This study aimed to assess the long-term oncologic outcomes of laparoscopy-assisted distal gastrectomy (LADG) versus laparoscopy-assisted total gastrectomy (LATG) for middle-third AGC. METHODS: A retrospective cohort study was conducted using data from 464 patients who underwent LADG or LATG between September 2007 and March 2013. Propensity score matching (PSM) were used for reducing the confounding effects to compare the long-term oncologic outcomes between two groups. Cox regression analysis was performed to clarify the prognostic factors. RESULTS: After PSM was performed, a well-balanced cohort of 376 patients (188 LADG and 188 LATG) was further analyzed. Of interest, the LADG group had a significantly shorter operative time (244.6 ±â€¯28.0 vs. 259.1 ±â€¯30.1, P < 0.0001), less operative blood loss (142.9 ±â€¯50.9 vs. 157.8 ±â€¯54.1, P = 0.006), earlier day of first flatus (2.6 ±â€¯0.8 vs. 2.9 ±â€¯0.9, P = 0.014), fewer number of retrieved lymph nodes (36.5 ±â€¯7.9 vs. 41.4 ±â€¯9.8, P < 0.0001), and shorter postoperative hospital stay (9.7 ±â€¯1.3 vs. 10.7 ±â€¯1.4, P < 0.0001) than the LATG group. However, no significant differences were observed in days of eating liquid diet (P = 0.626) and days of eating soft diet (P = 0.353). The incidence of overall and severe postoperative complications (Clavien-Dindo grade ≥ IIIa) following the LADG group were significantly fewer than the LATG group (overall, 24.5% vs. 34.6%, P = 0.032; severe, 4.8% vs. 11.2%, P = 0.022). In addition, the LADG group had significantly more favorable overall survival (OS) and disease-free survival (DFS) rates than the LATG group (5-year OS rate, 55.6% vs. 41.8%, P = 0.002; 5-year DFS rate, 45.9% vs. 32.8%, P < 0.001). In multivariate analyses, resection extent was not an independent prognostic factor for OS and DFS. CONCLUSIONS: This PSM cohort analysis has indicated LADG with D2 lymphadenectomy appeared to be safe and reasonable option for patients with middle-third AGC in general. LADG could contribute to improved survival.