Optimization of Minimum Segment Width Parameter in the Intensity-Modulated Radiotherapy Plan for Esophageal Cancer.

PURPOSE: This study was designed to explore the optimal minimum segment width (MSW) in the intensity-modulated radiotherapy (IMRT) plan for esophageal cancer. PATIENTS AND METHODS: The imaging data of 20 esophageal cancer patients were selected for this study. Four IMRT plans were designed for each patient with MSWs of 0.5, 1.0, 1.5, and 2.0 cm. The conformity index (CI) and homogeneity index (HI) of the planning target volumes (PTV), organs at risk (OARs), control points (CP), monitor units (MU), plan delivery time (DT), and gamma passing rates (GPR) were collected and compared to appraise the treatment plan quality and delivery efficiency. RESULTS: Lower-MSW plans had larger CI and smaller HI values, and lower dose parameters of OARs and PTVs. The HI, CI, and dose parameter of OARs in the 0.5 and 1.0 cm MSW groups were similar and much better than those of the 1.5 and 2.0 cm MSW groups. Meanwhile, the plan in the 0.5 cm MSW group had significantly higher MUs, CPs, and DTs, and a significantly lower relative dose of GPR with a 3% dose difference and 3 mm distance to agreement criteria than the other three groups. CONCLUSION: The 0.5 and 1 cm MSW groups had better dosimetric parameters and IMRT plan quality than the other groups. However, plans with 0.5 cm MSW had worse delivery accuracy and efficiency than the other three groups. Thus, MSW of 1.0 cm was the optimal choice to ensure good quality, delivery accuracy, and treatment efficiency in IMRT plans for esophageal cancer.

Retraction of "Nanostructured Lipid Carriers Delivering Sorafenib to Enhance Immunotherapy Induced by Doxorubicin for Effective Esophagus Cancer Therapy".

[This retracts the article DOI: 10.1021/acsomega.0c02072.].

Nanostructured Lipid Carriers Delivering Sorafenib to Enhance Immunotherapy Induced by Doxorubicin for Effective Esophagus Cancer Therapy.

The tumor microenvironment (TME) plays a significant role in weakening the effect of cancer immunotherapy, which calls for the remodeling of TME. Herein, we fabricated a nanostructured lipid carrier (NLC) to codeliver doxorubicin (Dox) and sorafenib (Sfn) as a drug delivery system (NLC/D-S). The Sfn was expected to regulate the TME of esophagus cancer. As a result, the immune response induced by Dox-related immunogenicity cell death could be fully realized. Our results demonstrated that Sfn was able to remodel the TME through downregulation of regulatory T cells (Treg), activation of effector T cells, and relieving of PD-1 expression, which achieved synergistic effect on the inhibition of primary tumor but also subsequent strong immune response on the regeneration of distant tumor.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

AFAP1-AS1 is upregulated and promotes esophageal squamous cell carcinoma cell proliferation and inhibits cell apoptosis.

Recent findings indicate that long noncoding RNAs (lncRNAs) were dysregulated in many kinds of tumors including esophageal squamous cell carcinoma (ESCC). LncRNA AFAP1-AS1 was found to be upregulated in hepatocellular carcinoma (HCC), lung cancer, colorectal cancer, esophageal adenocarcinoma (EAC), pancreatic ductal adenocarcinoma, and nasopharyngeal carcinoma, while its clinical value and potential function in ESCC are still unknown. Expression of AFAP1-AS1 was measured in 65 ESCC tissues and corresponding noncancerous tissues by quantitative real-time polymerase chain reaction, which revealed that AFAP1-AS1 expression was markedly elevated in ESCC tissues and significantly associated with advanced TNM stage (P = 0.004) and larger tumor size (P = 0.040). Moreover, by knocking down AFAP1-AS1 expression in ESCC cells, the proliferation and colony-forming ability were inhibited and cell apoptosis was induced. Our data indicated the first time that AFAP1-AS1, a novel oncogene, was remarkably upregulated and played a critical role in the progression of ESCC.

Influences of the interferon induced transmembrane protein 1 on the proliferation, invasion, and metastasis of the colorectal cancer SW480 cell lines.

BACKGROUND: Interferon-induced transmembrane protein 1 (IFITM1) has been identified as a molecular marker of the colorectal tumors; however its influences on the biological behaviors of the colorectal cancer cells are currently unknown. We aimed to study the influences of IFITM1 on the proliferation, invasion, and metastasis of the colorectal cancer SW480 cell lines. METHODS: We constructed IFITM1/pEGFP-C3 recombinant plasmids and transfected them into the colorectal cancer SW480 cell lines. IFITM1/pEGFP-C3 recombinant plasmids were identified by means of immunofluorescence, laser confocal scanning microscopy, and reverse transcription polymerase chain reaction. IFITM1/SW480 cells with stable over-expression of IFITM1 were confirmed by G418 screening. The influences of IFITM1 on the proliferation of the SW480 cell lines were investigated by MTT assay and tumor transplantation experiments in nude mice. Cell invasion experiments were performed to determine the invasion capacity of the IFITM1/SW480 cells. Matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were detected by the gelatin zymographic analysis, and MMP-9 expression by the Western blotting analysis. RESULTS: IFITM1/pEGFP-C3 recombinant plasmids were successfully constructed in this study, and the IFITM1/SW480 cells with stable IFITM1 gene over-expression were confirmed by G418 screening. MTT results showed that the proliferation of the IFITM1/SW480 cells was significantly enhanced (P < 0.01). Tumors were harvested from four weeks old mice. Tumor volumes were (1347.00 ± 60.94) mm(3), (1032.40 ± 111.38) mm(3) and (1018.78 ± 28.83) mm(3); and tumor weights were (1522.34 ± 62.76) mg, (1137.78 ± 97.22) mg and (1155.76 ± 133.31) mg for mice inoculated with the IFITM1/SW480 cells, pEGFP-C3/SW480 cells and SW480 cells, respectively. Tumor volumes and weights from mice inoculated with the IFITM1/SW480 cells were significantly increased (P < 0.01). In addition, the numbers of the SW480 cells and IFITM1/SW480 cells that migrated through Matrigel were 448.64 ± 38.09 and 540.45 ± 44.61, respectively; so the invasive ability of the SW480 cells transfected with IFITM1 gene was significantly greater than that of the SW480 cells (P < 0.01). Gelatin zymographic analysis showed that MMP-9 and MMP-2 protein activities in the IFITM1/SW480 cells were significantly enhanced, and Western blotting analysis showed that MMP-9 expression in the IFITM1/SW480 cells was also increased. CONCLUSION: IFITM1 can enhance the proliferation, invasion, and metastasis of the colorectal cancer SW480 cell lines.