Glioma s are the most common and malignant intracranial tumors in adults. Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments. However, access to comprehensive genomic data and analytical platforms is often limited. Here, we developed the Chinese Glioma Genome Atlas (CGGA), a user-friendly data portal for the storage and interactive exploration of cross-omics data, including nearly 2000 primary and recurrent glioma samples from Chinese cohort . Currently, open access is provided to whole-exome sequencing data (286 samples), mRNA sequencing (1018 samples) and microarray data (301 samples), DNA methylation microarray data (159 samples), and microRNA microarray data (198 samples), and to detailed clinical information (age, gender, chemoradiotherapy status, WHO grade, histological type, critical molecular pathological information, and survival data). In addition, we have developed several tools for users to analyze the mutation profiles, mRNA/microRNA expression, and DNA methylation profiles, and to perform survival and gene correlation analyses of specific glioma subtypes. This database removes the barriers for researchers, providing rapid and convenient access to high‐quality functional genomic data resources for biological studies and clinical applications. CGGA is available at http://www.cgga.org.cn .

Graphical AbstractHighlights d Characterization of the mutational landscape of secondary glioblastoma d Clonal and subclonal METex14 promote glioma progression and mark worse prognosis d PLB-1001 is a highly selective, efficient, and BBB-permeable MET kinase inhibitor d PLB-1001 provides a safe and efficacious therapeutic approach for glioma treatment SUMMARY Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying the mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and is present in $14% of cases with significantly worse prognosis. Subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. Furthermore, we describe a MET kinase inhibitor, PLB-1001, that demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in preclinical models. Importantly, this compound also shows blood-brain barrier permeability and is subsequently applied in a phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this therapy.

Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

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1Gliomas are the most common and malignant intracranial tumours in adults. Recent studies have 2 shown that functional genomics greatly aids in the understanding of the pathophysiology and 3 therapy of glioma. However, comprehensive genomic data and analysis platforms are relatively 4 limited. In this study, we developed the Chinese Glioma Genome Atlas (CGGA, 5 http://www.cgga.org.cn), a user-friendly data portal for storage and interactive exploration of multi-6 dimensional functional genomic data that includes nearly 2,000 primary and recurrent glioma 7 samples from Chinese cohorts. CGGA currently provides access to whole-exome sequencing (286 8 samples), messenger RNA sequencing (1,018 samples) and microarray (301 samples), DNA 9 methylation microarray (159 samples), and microRNA microarray (198 samples) data, as well as 10 detailed clinical data (e.g., WHO grade, histological type, critical molecular genetic information, 11 age, sex, chemoradiotherapy status and survival data). In addition, we developed an analysis tool to 12 allow users to browse mutational, mRNA/microRNA expression, and DNA methylation profiles and 13 perform survival and correlation analyses of specific glioma subtypes. CGGA greatly reduces the 14 barriers between complex functional genomic data and glioma researchers who seek rapid, intuitive, 15 and high-quality access to data resources and enables researchers to use these immeasurable data 16 sources for biological research and clinical application. Importantly, the free provision of data will 17 allow researchers to quickly generate and provide data to the research community. 18 19

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The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin β3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas.