ObjectiveTumour heterogeneity represents a major obstacle to accurate diagnosis and treatment in gastric adenocarcinoma (GA). Here, we report a systematic transcriptional atlas to delineate molecular and cellular heterogeneity in GA using single-cell RNA sequencing (scRNA-seq).DesignWe performed unbiased transcriptome-wide scRNA-seq analysis on 27 677 cells from 9 tumour and 3 non-tumour samples. Analysis results were validated using large-scale histological assays and bulk transcriptomic datasets.ResultsOur integrative analysis of tumour cells identified five cell subgroups with distinct expression profiles. A panel of differentiation-related genes reveals a high diversity of differentiation degrees within and between tumours. Low differentiation degrees can predict poor prognosis in GA. Among them, three subgroups exhibited different differentiation grade which corresponded well to histopathological features of Lauren’s subtypes. Interestingly, the other two subgroups displayed unique transcriptome features. One subgroup expressing chief-cell markers (eg, LIPF and PGC) and RNF43 with Wnt/β-catenin signalling pathway activated is consistent with the previously described entity fundic gland-type GA (chief cell-predominant, GA-FG-CCP). We further confirmed the presence of GA-FG-CCP in two public bulk datasets using transcriptomic profiles and histological images. The other subgroup specifically expressed immune-related signature genes (eg, LY6K and major histocompatibility complex class II) with the infection of Epstein-Barr virus. In addition, we also analysed non-malignant epithelium and provided molecular evidences for potential transition from gastric chief cells into MUC6+TFF2+ spasmolytic polypeptide expressing metaplasia.ConclusionAltogether, our study offers valuable resource for deciphering gastric tumour heterogeneity, which will provide assistance for precision diagnosis and prognosis.
BackgroundGastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored areas of precision medicine. In this study, we aimed to establish an in vivo patient-derived xenograft (PDX) model based on zebrafish (Danio rerio) embryos, allowing for a rapid analysis of the angiogenic and invasive potentials, as well as a fast drug sensitivity testing.MethodsTwo human gastric cancer cell lines (AGS and SGC-7901) were xenografted into zebrafish embryos, their sensitivity to 5-FU were tested both in vitro and in vivo. Fourteen human primary cells from gastric cancer tissue were xenografted into zebrafish embryos, their proliferating, angiogenic and metastatic activities were evaluated in vivo. Sensitivity to 5-FU, docetaxel, and apatinib were also tested on primary samples from four patients.ResultsSGC-7901 showed higher sensitivity to 5-FU than AGS both in vitro (6.3 ± 0.9 μM vs.10.5 ± 1.8 μM) and in vivo. Nine out of fourteen patient samples were successfully transplanted in zebrafish embryos and all showed proliferating, angiogenic and metastatic potentials in the living embryos. Four cases showed varied sensitivity to the selected three chemotherapeutic drugs.ConclusionsOur zebrafish PDX (zPDX) model is a preclinically reliable in vivo model for GC. The zPDX model is also a promising platform for the translational research and personalized treatment on GC.Electronic supplementary materialThe online version of this article (10.1186/s13046-017-0631-0) contains supplementary material, which is available to authorized users.
The
discovery and prosperous growth of synthetic polymers have
presented both significant advantages and daunting challenges in the
last century. To address the issues of environmental pollution and
fossil consumption, recyclable, degradable, and/or biobased polymers
have been given much attention in the polymer science community. This
viewpoint focuses on the emerging fully chemical recyclable poly(γ-butyrolactone)-based
polymers. The breakthrough from nonpolymerizable to efficient polymerization
is highlighted by the benefits of the development of a series of catalysis
for ring-opening polymerization of γ-butyrolactone. Subsequently,
the design of γ-butyrolactone derivatives and synthesis of more
recyclable polymers are summarized together with the discussions about
the structure and property relationship. Finally, the remaining challenges
and promising opportunities are suggested in order to provide insights
into the further direction for sustainable polymers.
Background
Extremity myxoid liposarcoma (MLS) is a rare soft tissue sarcoma in adults. We performed this study to define distinctive clinical features of extremity MLS by assessing prognostic factors.
Methods
Between 1973 and 2015, 1756 patients with extremity MLS who underwent surgical resection were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute. Both overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method (to obtain OS and CSS curves) and a Cox proportional hazards regression model.
Results
Of the 1756 patients with extremity MLS, the mean and median patient age at diagnosis were 47 and 45 years, respectively. More than half (
n
= 1027, 58.5%) of the patients were male. In terms of location, 10.5% tumors were located in the upper limbs and 89.5% in lower limbs. All patients received local surgery, and about half of the patients (57.2%) received radiation treatment. The 5- and 10-year OS rates of the entire cohort were 86.4% and 75.9%, respectively. The 5- and 10-year CSS rates were 90.5% and 85.2%, respectively. On multivariate analysis, older age, male gender, high tumor grade, and tumor size > 10 cm were found to be independent risk factors of both decreased OS and CSS. Year of diagnosis ≥ year 2000 was significantly associated with an increased CSS. In addition, radiation treatment failed to become an independent risk factor for either OS or CSS.
Conclusion
We identified age, gender, tumor grade, year of diagnosis, and tumor size as independent prognostic factors for OS and CSS in patients with extremity MLS.
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