GBAP1 functions as a tumor promotor in hepatocellular carcinoma via the PI3K/AKT pathway

Abstract Hepatocellular carcinoma (HCC) is common worldwide, and novel therapeutic targets and biomarkers are needed to improve outcomes. In this study, bioinformatics analyses combined with in vitro and in vivo assays were used to identify the potential therapeutic targets. Differentially expressed genes (DEG) in HCC were identified by the intersection between The Cancer Genome Atlas and International Cancer Genome Consortium data. The DEGs were evaluated by a gene set enrichment analysis as well as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A protein interaction network, univariate Cox regression, and Lasso regression were used to screen out hub genes correlated with survival. Increased expression of the long noncoding RNA GBAP1 in HCC was confirmed in additional datasets and its biological function was evaluated in HCC cell lines and nude mice. Among 121 DEGs, GBAP1 and PRC1 were identified as hub genes with significant prognostic value. Overexpression of GBAP1 in HCC was confirmed in 21 paired clinical tissues and liver cancer or normal cell lines. The inhibition of GBAP1 expression reduced HCC cell proliferation and promoted apoptosis by inactivating the PI3K/AKT pathway in vitro and in vivo. Therefore, GBAP1 has a pro-oncogenic function in HCC and is a candidate prognostic biomarker and therapeutic target

Folate/NIR 797-conjugated albumin magnetic nanospheres: synthesis, characterisation, and in vitro and in vivo targeting evaluation.

A practical and effective strategy for synthesis of Folate-NIR 797-conjugated Magnetic Albumin Nanospheres (FA-NIR 797-MAN) was developed. For this strategy, Magnetic Albumin Nanospheres (MAN), composed of superparamagnetic iron oxide nanoparticles (SPIONs) and bovine serum albumin (BSA), were covalently conjugated with folic acid (FA) ligands to enhance the targeting capability of the particles to folate receptor (FR) over-expressing tumours. Subsequently, a near-infrared (NIR) fluorescent dye NIR 797 was conjugated with FA-conjugated MAN for in vivo fluorescence imaging. The FA-NIR 797-MAN exhibited low toxicity to a human nasopharyngeal epidermal carcinoma cell line (KB cells). Additionally, in vitro and in vivo evaluation of the dynamic behaviour and targeting ability of FA-NIR 797-MAN to KB tumours validated the highly selective affinity of FA-NIR 797-MAN for FR-positive tumours. In summary, the FA-NIR 797-MAN prepared here exhibited great potential for tumour imaging, since the near-infrared fluorescence contrast agents target cells via FR-mediated endocytosis. The high fluorescence intensity together with the targeting effect makes FA-NIR 797-MAN a promising candidate for imaging, monitoring, and early diagnosis of cancer at the molecular and cellular levels

Facile assembly of upconversion nanoparticle-based micelles for active targeted dual-mode imaging in pancreatic cancer

Abstract Background Pancreatic cancer remains the leading cause of cancer-related deaths, the existence of cancer stem cells and lack of highly efficient early detection may account for the poor survival rate. Gadolinium ion-doped upconversion nanoparticles (UCNPs) provide opportunities for combining fluorescent with magnetic resonance imaging, and they can improve the diagnostic efficacy of early pancreatic cancer. In addition, as one transmembrane glycoprotein overexpressed on the pancreatic cancer stem cells, CD326 may act as a promising target. In this study, we developed a facile strategy for developing anti-human CD326-grafted UCNPs-based micelles and performed the corresponding characterizations. After conducting in vitro and vivo toxicology experiments, we also examined the active targeting capability of the micelles upon dual-mode imaging in vivo. Results We found that the micelles owned superior imaging properties and long-time stability based on multiple characterizations. By performing in vitro and vivo toxicology assay, the micelles had good biocompatibility. We observed more cellular uptake of the micelles with the help of anti-human CD326 grafted onto the micelles. Furthermore, we successfully concluded that CD326-conjugated micelles endowed promising active targeting ability by conducting dual-mode imaging in human pancreatic cancer xenograft mouse model. Conclusions With good biocompatibility and excellent imaging properties of the micelles, our results uncover efficient active homing of those micelles after intravenous injection, and undoubtedly demonstrate the as-obtained micelles holds great potential for early pancreatic cancer diagnosis in the future and would pave the way for the following biomedical applications

Prussian blue-stained in tumor tissue of nude mice with nasopharyngeal carcinoma after administration of (a) FA-NIR 797-MAN, (b) NIR 797-MAN and (c) FA-NIR-797-MAN+FA at 72 h injection (×200 magnification) (the arrow indicates the blue-stained iron particles).

<p>Prussian blue-stained in tumor tissue of nude mice with nasopharyngeal carcinoma after administration of (a) FA-NIR 797-MAN, (b) NIR 797-MAN and (c) FA-NIR-797-MAN+FA at 72 h injection (×200 magnification) (the arrow indicates the blue-stained iron particles).</p

Magnetization curve as a function of field for MAN and FA-MAN at a temperature of 25°C.

<p>Magnetization curve as a function of field for MAN and FA-MAN at a temperature of 25°C.</p

Ex vivo NIR imaging of three groups at 72 h intervals after administration of (a) FA-NIR 797-MAN, (b) NIR 797-MAN and (c) FA-NIR-797-MAN+FA.

<p>Ex vivo NIR imaging of three groups at 72 h intervals after administration of (a) FA-NIR 797-MAN, (b) NIR 797-MAN and (c) FA-NIR-797-MAN+FA.</p

DLS measurement of FA-NIR 797-MAN nanospheres.

<p>(a) The graph shows size distribution of of FA-NIR 797-MAN nanospheres in water. (b) Average hydrodynamic diameter change of FA-NIR 797-MAN when incubating in water at 4°C for 7 days.</p

Absorption spectra of (A) FA-MAN, (B) MAN and (C) FA.

<p>Absorption spectra of (A) FA-MAN, (B) MAN and (C) FA.</p