Background/Aim: Radiation (RT) induced ERK/NF-ĸB in hepatocellular carcinoma (HCC) has been reported in our previous works; it weakens the toxicity of RT or triggers a radioresistance effect. Thus, combining RT with a suitable NF-ĸB inhibitor may sensitize HCC to RT. Magnolol, a bioactive compound, was known to have antiinflammatory and anti-tumor functions. Here, we aimed to investigate whether magnolol may enhance anti-HCC efficacy of RT in vivo. Materials and Methods: We established a Hep3B bearing mouse to evaluate the efficacy of the combination treatment of magnolol and RT. Results: Most significantly, tumor volume and tumor weight inhibition was found in the combination group. Tumor immunohistochemistry staining also illustrated the suppression of RT-induced ERK/NF-ĸB-related proteins expression by magnolol. In addition, intrinsic apoptosis-related proteins, such as caspase-3 and-9, were markedly increased in the combination group. Conclusion: Magnolol may effectively enhance anti-HCC ability of RT by downregulating the expression of ERK/NF-ĸB-related proteins and increasing the expression of apoptosis-related proteins. Hepatocellular carcinoma (HCC), the most common type of liver cancer in adults, ranks as the fourth leading cause of cancer-related mortality worldwide (1). Patients with advanced HCC are unsuitable candidates for curative treatment options including surgery, liver transplantation, and percutaneous ablation (2). The low tolerance of whole liver to radiation has restricted application of radiotherapy (RT) for HCC in the past. Recent technology advancements in RT such as intensitymodulated RT (IMRT), image-guided RT (IGRT), hypofractionated radiotherapy (HFRT), and stereotactic body RT (SBRT) can precisely deliver high-dose radiation to HCC while reducing noncancerous liver tissue irradiation (3-5). RT

1485 Recombinant human granulocyte colony-stimulating factors (rhG-CSF) including filgrastim, lenograstim and pegfilgrastim are widely used to treat chemotherapy-induced neutropenia. However, it remains a challenge to manage severe neutropenia in cancer patients after high dose chemotherapy. The activation of G-CSFR by the G-CSF requires dimerization of two receptor chains bound to two G-CSF ligands. We hypothesized that a G-CSF dimer might generate a faster in vivo response, thus to benefit patients with severe neutropenia. F-627 is a recombinant human G-CSF dimer expressed in mammalian cells. In vitro, F-627 was able to activate STAT3 and to stimulate the proliferation of 32D-GCSFR and M-NSF60 cell lines. To evaluate the efficacy of F-627 in chemotherapy-induced neutropenia, 36 adult cynomolgus monkeys (3/sex) were injected with cyclophoshamide (CY, i.v., 60 mg/kg on day 0 and 65 mg/kg on day 1). Animals were randomized to receive (s.c.) either carrier, or F-627 on day 5 and day 10, at 25, 60 and 150 μg/kg, or rhG-CSF at 10 μg/kg /day (daily injection), or pegfilgrastim at 60 μg/kg on day 5 and day 10. Pharmacokinetics and pharmacodynamics (PK/PD) were evaluated. Significant absolute neutrophil count (ANC) increase was observed in animals treated with F-627 at 25 μg/kg compared to carrier-treated monkeys. At nadir, F-627 at 60 μg/kg generated optimal ANC response with 6.9- and 3.0-fold higher ANC compared to pegfilgrastim- (0.17 × 109/L) and rhG-CSF- (0.39 × 109/L) treated monkeys, respectively. The PK parameters of F627 at 60 ug/kg including MRT, Cmax, Tmax, AUC and CL were comparable to that of pegfilgrastim-treated monkeys, despite the relative G-CSF molar dose in F-627-treated animals was 2.5x lower than the pegfilgrastim-treated animals. The results demonstrate that the G-CSF dimer generated a faster response in CY-treated monkeys compared to the G-CSF monomer-treated animals, suggesting that F-627 could benefit cancer patients with severe neutropenia after high-dose chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Superparamagnetic iron oxide (SPIO) has been used as a contrast agent for magnetic resonance imaging (MRI) since the late 20th century. With the development of SPIO, cellular MRI has been recognized as a suitable and highly sensitive noninvasive modality with great potential to benefit translational research. In addition to its traditional diagnostic property, latest advances have conferred SPIO with multifunctionality. Several SPIO-based theranostic probes with targeting, therapeutic and diagnosis components have been successfully developed. The objective of this brief review is to summarize the characteristics, synthesizing methods, labeling approaches and current applications of SPIO-based cellular MRI in oncology. Herein, we first depict the history, classification and advantages of and the differences between T1- and T2/T2*-based SPIO contrast agents for cancer treatment. Second, we outline current coating materials that render SPIO less toxic and more biocompatible to mammalian cells. Finally, the cell labeling techniques and applications of SPIO-based MRI for tracking mesenchymal stem cell tumor–homing in preclinical models are introduced.

4722 The management of severe neutropenia in cancer patients after high-dose chemotherapy remains a challenge, although recombinant human G-CSFs including filgrastim, lengogratim and pegfilgrastim have been widely used. We developed F-627, a mammalian expressed recombinant human G-CSF dimer to treat severe neutropenia. In a cyclophosphamide-induced neutropenia monkey model, F-627 significantly reduced the duration and lessened the severity of neutropenia compared to monkeys treated with G-CSF or pegylated G-CSF. We report the phase I results of F-627 in healthy male subjects receiving ascending single dose at 30, 60, 120 and 240 ug/kg by subcutaneous injection. The primary objective of the phase I study was to assess the safety and tolerability of F-627. The secondary objective was to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) responses. F-627 was well tolerated in healthy male volunteers. Dose-dependent PD responses including increased WBC, ANC and CD34 levels in peripheral blood were demonstrated. These results indicate that the mechanism of action of F-627 is similar to the monomer recombinant hG-CSFs, while the mode of action of F-627 is different with unique PK/PD properties in human. Disclosures: No relevant conflicts of interest to declare.