visualization-quantification-brown-beige-adipose-tissues-mice-using

Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [<sup>18</sup>F]FDG Micro-PET/MR Imaging

Brown and beige adipocytes are now recognized as potential therapeutic targets for obesity and metabolic syndromes. Non-invasive molecular imaging methods ...

non-invasive-petmr-imaging-an-orthotopic-mouse-model-hepatocellular

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and ...

The University of Hong Kong

University of Oxford

Most tumor cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and promote tumorigenicity and drug resistance. Intriguingly, the molecular mechanisms underlying this phenomenon are not well understood. In this work, using gain-of-function and loss-of-function in vitro studies in patient-derived organoid and cell cultures as well as in vivo positron emission tomography-magnetic resonance imaging animal models, we showed that protein arginine N-methyltransferase 6 (PRMT6) regulates aerobic glycolysis in human hepatocellular carcinoma (HCC) through nuclear relocalization of pyruvate kinase M2 isoform (PKM2), a key regulator of the Warburg effect.

CRAF Methylation by PRMT6 Regulates Aerobic Glycolysis-Driven Hepatocarcinogenesis via ERK-Dependent PKM2 Nuclear Relocalization and Activation.

Targeting of PARP enzymes has emerged as an effective therapeutic strategy to selectively target cancer cells with deficiencies in homologous recombination signaling. Currently used to treat -mutated cancers, PARP inhibitors (PARPi) have demonstrated improved outcome in various cancer types as single agents. Ongoing efforts have seen the exploitation of PARPi combination therapies, boosting patient responses as a result of drug synergisms. Despite great successes using PARPi therapy, selecting those patients who will benefit from single agent or combination therapy remains one of the major challenges. Numerous reports have demonstrated that the presence of a  mutation does not always result in synthetic lethality with PARPi therapy in treatment-naïve tumors. Cancer cells can also develop resistance to PARPi therapy. Hence, combination therapy may significantly affect the treatment outcomes. In this review, we discuss the development and utilization of PARPi in different cancer types from preclinical models to clinical trials, provide a current overview of the potential uses of PARP imaging agents in cancer therapy, and discuss the use of radiolabeled PARPi as radionuclide therapies.

PARP Inhibitors in Cancer Diagnosis and Therapy.

Transarterial chemoembolization is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). This study evaluated the anti-tumor effect of the semi-interpenetrating network (IPN) hydrogel as a novel embolic material for trans-portal vein chemoembolization (TPVE) . A nude mice orthotopic HCC model was established, followed by TPVE using IPN hydrogel loaded with or without cisplatin. Portal vein blockade was visualized by MRI and the development of tumor was monitored by IVIS Spectrum Imaging. Tumor proliferation and angiogenesis were evaluated by Ki67 and CD34 staining respectively. Intra-tumor caspase 3, Akt, ERK1/2, and VEGF activation were detected by Western Blot. F-FMISO uptake was evaluated by microPET-MRI scanning. IPN hydrogel first embolized the left branch of portal vein within 24 hours and further integrated into the intra-tumor vessels during 2 weeks after the treatment. Mice treated with cisplatin-loaded hydrogels exhibited a significant decrease in tumor growth, along with lower plasma AFP levels as compared to hydrogel-treated and untreated tumor-bearing mice. By Ki67 and CD34 staining, the TPVE with IPN hydrogel suppressed tumor proliferation and angiogenesis. In addition, increased tumor apoptosis shown by up-regulation of caspase 3 with decreased expressions of tumor cell survival indicators Akt and ERK1/2 were observed in the treatment groups. Consistent with the decreased expression of VEGF after TPVE, hypoxia level in the tumor was also reduced as indicated by F-FMISO uptake level. IPN hydrogel-based TPVE significantly suppressed the tumor development by regulating intra-tumor angiogenesis and cell survival in an orthotopic HCC mouse model, suggesting a viable embolic agent for transarterial chemoembolization.

Kel Vin Tan

Department of Diagnostic Radiology,
Li Ka Shing Faculty of Medicine,
School of Clinical Medicine,
LKS Faculty of Medicine,
Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine

The University of Hong Kong

Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [¹⁸F]FDG Micro-PET/MR Imaging

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Kel Vin Tan

Department of Diagnostic Radiology,Li Ka Shing Faculty of Medicine,School of Clinical Medicine,LKS Faculty of Medicine,Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine

The University of Hong Kong

Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Department of Diagnostic Radiology,
Li Ka Shing Faculty of Medicine,
School of Clinical Medicine,
LKS Faculty of Medicine,
Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine

Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [¹⁸F]FDG Micro-PET/MR Imaging