Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3 0 -untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

We conducted a retrospective analysis to assess the toxicity and long-term survival of esophageal squamous cell carcinoma patients treated with three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2DRT). All data in the present study were based on four prospective clinical trials conducted at our institution from 1996 to 2004 and included 308 esophageal squamous cell carcinoma patients treated with 2DRT or 3DCRT/IMRT. Based on the inclusion and exclusion criteria, 254 patients were included in the analysis. Of these patients, 158 were treated with 2DRT, whereas 96 were treated with 3DCRT/IMRT. The rates of ≥Grade3 acute toxicity of the esophagus and lung were 11.5% versus 28.5% (P = 0.002) and 5.2% versus 10.8% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The incidences of ≥Grade 3 late toxicity of the esophagus and lungs were 3.1% versus 10.7% (P = 0.028) and 3.1% versus 5.7% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The 1-year, 3-year and 5-year estimated overall survival rates were 81%, 38% and 34% in the 3DCRT/IMRT group and 79%, 44% and 31% in the 2DRT group, respectively (P = 0.628). The 1-year, 3-year and 5-year local control rates were 88%, 71% and 66% in the 3DCRT/IMRT group and 84%, 66% and 60% in the 2DRT group, respectively (P = 0.412). Fewer incidences of acute and late toxicities were observed in esophageal squamous cell carcinoma patients treated with 3DCRT/IMRT compared with those treated with 2DRT. No significant survival benefit was observed with the use of 3DCRT/IMRT.

Background: Anti-PD-1 antibody had showed encouraging activity as salvage treatment in pts with certain subtypes of advanced soft tissue sarcoma (STS). However, its role in first-line setting is uncertain. We assessed the safety and activity of sintilimab, an anti-PD-1 antibody, combined with AI in pts with certain subtypes of advanced STS.Methods: This is a single-arm, phase 2 study. Systemic treatment naïve pts with metastatic or unresectable locally advanced undifferentiated pleomorphic sarcoma(UPS), synovial sarcoma (SS), myxoid Liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS) were treated with sintilimab (200mg, d1), doxorubicin (60mg/ m 2 , d1); and ifosfamide (1.8 g/m 2 /d, d1-5) every 3 weeks for up to 6 cycles, followed by sintilimab maintenance until disease progression, unacceptable toxicities or up to 2 years. Based on a Simon 2-stage design, first 17 pts with 5 responses are required for the 1 st stage and additional 24 pts for the 2 nd stage. A safety run-in phase was conducted in the first 6 enrolled pts to assess the safety and tolerability by predefined dose limiting toxicity (DLT). The primary endpoint was objective response rate (ORR, per RECIST 1.1), and secondary endpoints included progression free survival (PFS), overall survival (OS) and safety.Results: As of August 31, 2021, 24 pts were enrolled. 13 were male, and the median age was 48. Median follow-up was 3.8 months (range 0.4-14.2). Of the 16 evaluable pts, ORR was 62.5% (10/16, 1 unconfirmed SS), including 1/1(100%) UPS, 6/7 (85.7%) SS, 2/2 (100%) MLPS and 1/6 (16.7%) DDLPS pts, which met the 1 st stage threshold for expanding erollment. 1 DLT (grade 4 neutropenia, infection) was observed in the first 6 patients during the DLT observation window. The most frequent grade 3 adverse events included leucopenia (41.7%), neutropenia (33.3%), thrombocytopenia (29.2%), anaemia (16.7%) and 1 grade 5 respiratory failure. No immune-related SAEs were observed.Conclusions: The primary endpoint of ORR was met for the 1st stage which indicated expected efficacy of this combination. Enrolment of the 2nd stage is ongoing to further investigate the efficacy and safety of sintilimab combined with AI in the firstline treatment of UPS, SS, MLPS and DDLPS.