A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma.

Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation.

FTO blocks RNA translational activity via the loss of N6-methyladenosine methylation at 5' UTR regulated by RBM5 in cisplatin-resistant NSCLC.

N6-methyladenosine (m6A) methylation has been widely regarded in numerous biological functions including CR. Nonetheless, the molecular process of m6A methylation behind CR in non-small cell lung cancer (NSCLC) has no apparent significance. We identified in this study that the expression of FTO alpha-ketoglutarate dependent dioxygenase (FTO) was downregulated in CR NSCLC tissues and cells in vivo and in vitro.

Efferocytosis: An accomplice of cancer immune escape.

The clearance of apoptotic cells by efferocytes such as macrophages and dendritic cells is termed as "efferocytosis", it plays critical roles in maintaining tissue homeostasis in multicellular organisms. Currently, available studies indicate that efferocytosis-related molecules and pathways are tightly associated with cancer development, metastasis and treatment resistance, efferocytosis also induces an immunosuppressive tumor microenvironment and assists cancer cells escape from immune surveillance. In this study, we reviewed the underlying mechanisms of efferocytosis in mediating the occurrence of cancer immune escape, and then emphatically summarized the strategies of using efferocytosis as therapeutic target to enhance the anti-tumor efficacies of immune checkpoint inhibitors, hoping to provide powerful evidences for more effective therapeutic regimens of malignant tumors.

Knockdown of CHCHD2 inhibits migration and angiogenesis of human renal cell carcinoma: A potential molecular marker for treatment of RCC.

Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), a novel cell migration determinant, is able to co-express with other genes of the oxidative phosphorylation pathway by using a computational expression screening technique. However, little is known about the expression and biological function of CHCHD2 in human renal cell carcinoma (RCC). Western blotting was performed to detect CHCHD2 expression levels in normal renal cells and carcinoma cells.

Rap2B promotes angiogenesis via PI3K/AKT/VEGF signaling pathway in human renal cell carcinoma.

Human renal cell carcinoma which is a highly vascular tumor is the leading cause of death from urologic cancers. Angiogenesis has a pivotal role in oncogenesis and in the viability and expansion of renal cell carcinoma. Rap2B, as a small guanosine triphosphate-binding protein of the Ras family, was first discovered in the early 1990s during the screening of a platelet complementary DNA library.

Structure, functional regulation and signaling properties of Rap2B.

The Ras family small guanosine 5'-triphosphate (GTP)-binding protein Rap2B is is a member of the Ras oncogene family and a novel target of p53 that regulates the p53-mediated pro-survival function of cells. The Rap2B protein shares ~90% homology with Rap2A, and its sequence is 70% identical to other members of the Rap family such as RaplA and RaplB. As a result, Rap2B has been theorized to have similar signaling effectors to the GTPase-binding protein Rap, which mediates various biological functions, including the regulation of sterile 20/mitogen-activated proteins.

Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway.

Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of tumors and promotes migration and invasion of human suprarenal epithelioma. However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B was examined in breast cancer cell lines and human normal breast cell line using Western blot analysis.

Role of Rap2 and its Downstream Effectors in Tumorigenesis.

Rap2, a member of the GTP-binding proteins, is widely upregulated in many types of tumors. The specific effectors of Rap2 can affect multiple cancer-associated cellular processes, including cytoskeleton reorganization, proliferation, migration, and inflammation. However, the functional role of Rap2 in tumorigenesis and the interplay between different effectors remain to be fully elucidated.

p53 target gene Rap2B regulates the cytoskeleton and inhibits cell spreading.

Purpose: Cell migration requires spatiotemporal integration of signals that target cytoskeletal. Previous studies have indicated that Rho GTPases are crucial regulators of actin dynamics. As homologs of Rho proteins, the role of Rap2B in the regulation of cytoskeleton and its cell signaling pathway remains unknown.

Rap2B promotes migration and invasion of human suprarenal epithelioma.

The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously.