Surgery versus radiotherapy for limited-stage small cell esophageal carcinoma: a multicenter, retrospective, cohort study in China (ChiSCEC).

BACKGROUND: There is no standard management for small cell esophageal carcinoma (SCEC). The purpose of this multicenter, retrospective study (ChiSCER) was to investigate the treatment, outcomes, and risk factors impacting survival endpoints in patients with limited-stage SCEC (LS-SCEC). MATERIALS AND METHODS: Consecutive patients with LS-SCEC from 14 institutions between 2000 and 2020 in China were enrolled. Survival curves were constructed using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate Cox regression models and propensity score matching (PSM) analysis were adopted in the prognostic analysis. Results were reported as hazard ratio (HR), 95% confidence interval (CI), and P value. Statistical significance was set as P value <0.05 in a two-tailed test. RESULTS: Among 458 LS-SCEC patients, the median age was 63 [interquartile range (IQR), 57-68] years, and 318 (69%) were males. Eighty-four (18%), 167 (36%), and 207 (45%) patients received chemotherapy (CT) alone, CT plus definitive radiotherapy (CT+RT), and CT plus radical surgery (CT+S), respectively. With a median follow-up time of 58.7 (95% CI 48.9-68.6) months, the median overall survival (OS) and 3-year OS rate for all patients 24.3 (95% CI 21.6-27) months and 37.3% (95% CI 32.8-42.5%), respectively. Multivariate analysis indicated that treatment modes, Karnofsky performance status (KPS), TNM stage, and CT cycle were independent prognostic factors for OS ( P <0.05). Compared with CT alone, patients treated with CT+RT (HR 0.57, 95% CI 0.41-0.8, P =0.001) or CT+S (HR 0.59, 95% CI 0.42-0.82, P =0.002) had an improved OS, with no significant survival differences between CT+S and CT+RT groups after multivariate and PSM analyses ( P >0.05). Subgroup analysis indicated that compared with CT+RT, patients with tumor location at lower 1/3 (HR 0.59, 95% CI 0.37-0.93, P =0.03) or tumor length >5 cm (HR 0.52, 95% CI 0.3-0.9, P =0.02) could obtain significant OS benefit from CT+S. Patients with tumor location at middle 1/3 (HR 1.55, 95% CI 1.03-2.36, P =0.04) or tumor length ≤5 cm (HR 1.49, 95% CI 1.02-2.17, P =0.04) favored CT+RT. Distant metastasis accounted for 73.7% of all treatment failures after multidisciplinary treatments. CONCLUSION: Surgery and RT were equally effective local therapies for patients with LS-SCEC. The personalized decision of local therapy should be made after comprehensive considerations on tumor location, length, comorbidities, and organ preservation.

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR-382-5p/YB-1 axis.

Circular RNA (circRNA) can modulate the gene expression via sponging microRNA (miRNA) in multiple malignancies. Nevertheless, the detailed function of circ_0001658 in osteosarcoma (OS) and its regulatory mechanism remain elusive. Real-time PCR was carried out to detect the expressions of circ_0001658, miR-382-5p, and Y box-binding protein 1 (YB-1) mRNA in OS tissues. Besides, western blot was done to monitor YB-1 expression in OS cells. Chi-squared test was used to analyse the correlation between circ_0001658 and clinicopathologic characteristics of OS patients. CCK8 assay, colony formation assay, flow cytometry, and transwell assay were performed to determine the function of circ_0001658. Moreover, dual-luciferase reporter gene assay was done to verify the targeting relationship between circ_0001658 and miR-382-5p. Compared with adjacent tissues, circ_0001658 displayed a significantly higher expression in OS tissues. Circ_0001658 could facilitate the proliferation, migration, and invasion of OS cells and impede apoptosis by sponging miR-382-5p. Further, circ_0001658 was proved to directly and negatively regulate the expression of miR-382-5 while positively modulate the expression of YB-1. Circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. SIGNIFICANCE OF THE STUDY: In recent years, the expression and function of circular RNA in cancer have been the focus of tumour research. The study on circular RNA helps elucidate the molecular pathology of tumorigenesis and cancer progression. This study demonstrated that circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. To our best knowledge, this work is the first to study the expression and function of circ_0001658 in cancer.

NIR absorbing reduced graphene oxide for photothermal radiotherapy for treatment of esophageal cancer.

Theranostic agents were drawing a huge attention in the personalized medication. In this study, we established a facile technique, plant extract-based technique for the synthesis of reduced nano-graphene oxide (RNGO) with low cytotoxicity. We formed platforms of photothermal (PT) therapy and further explained that the synthesized RNGO can be utilized as ready to use PT therapy without any additional surface adjustment. In the meantime, with the help of a constant-wave NIR laser (near-infrared), in vitro esophageal adenocarcinoma cell line (OE-19) cancer cells were effectively ablated, because of the PT impact of RNGO. The outcomes propose that the RNGO was appropriate for PT therapy and photoacoustic imaging of the tumor, which is assuring for theranostic nanomedicine.

Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways.

In previous years, progranulin (PGRN) has attracted increasing attention due to its oncogenic roles in several types of tumor. However, the clinical relevance of PGRN in gastric cancer remains to be elucidated. In the present study, 120 retrospective tissue samples were obtained from patients with primary gastric cancer, and the expression of PGRN was detected using immunohistochemistry. The results showed that 71 cases exhibited a high expression of PGRN, which was markedly higher than the 49 cases with a low expression of PGRN. Subsequent χ2 analysis confirmed for the first time, to the best of our knowledge, that a high level of PGRN was positively correlated with lymph node metastasis (P=0.048), lymphatic invasion (P=0.018) and advanced clinical stage (P=0.027). Survival analysis showed that PGRN was positively correlated with poorer overall survival (OS; P=0.0043) and progression­free survival (PFS; P=0.0022). Univariate and multivariate Cox regression analysis showed that PGRN and clinical stage had a significant effect on the OS and PFS of the patients with gastric cancer. In addition, cell experiments confirmed that extracellular PGRN promoted the intracellular expression of PGRN in a concentration­dependent manner in gastric cancer cells. The AKT and extracellular signal­regulated kinase signaling pathways were involved in the upregulation of intracellular PGRN induced by extracellular PGRN in MKN­45 and MGC­803 gastric cancer cells. Taken together, the results of the present study suggested that PGRN may be important in the progression and prognosis of gastric cancer, and that the expression of PGRN was regulated in a positive feedback loop. These findings enhance current knowledge regarding PGRN in tumors.