Prognostic value of 18F-FDG PET for hepatocellular carcinoma patients treated with sorafenib.

BACKGROUND: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used (18) F-2-fluoro-2-deoxyglucose ((18) F-FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC. MATERIALS AND METHODS: A total of 29 patients with HCC were included. Baseline (18) F-FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient. RESULTS: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0-12.0] and 3.8 months (95% CI: 1.4-6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α-fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors (P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too (P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax (n=10; <5.00) and high SUVmax (n=19;≥ 5.00), the low SUV group showed significantly longer OS and PFS (P=0.023 and P=0.042 respectively). CONCLUSION: Our study showed that the degree of FDG uptake is an independent prognostic factor in patients with HCC who undergo sorafenib treatment.

Oral administration of aqueous extract of Carthami Flos induces macrophage activation and preferentially potentiates type 1 helper T-cell response in vivo.

In vivo immunomodulatory activity of aqueous extract of Carthami Flos (AECF) was investigated using a mouse model immunized with keyhole limpet hemocyanin. Serum level of Ag-specific IgG2a was significantly elevated by oral administration of AECF but not IgG1. However, no selective B-cell proliferation by AECF was observed in vivo. Ag-specific proliferation and IFN-gamma and IL-5 production of draining lymph node T cells also was higher in AECF-treated mice when compared with water-treated control mice. However, AECF failed to enhance nonspecific T-cell response under CD3 stimulation. These results led us to hypothesize that AECF potentiates Ag-specific T-cell response, possibly through activation of antigen presenting cells (APC) other than B cells. Functional assessment of splenic macrophages showed that AECF administration significantly enhances IL-12 production as well as APC activity for IFN-gamma production and STAT-4 activation by T cells. Collectively, these data strongly support that AECF preferentially potentiates immune response polarized toward TH1 and for which increased activation of macrophages is most likely to be responsible. The present data implicate a possible application of AECF to potentiate cellular immunity and, we hope, prevent intracellular infections.

Effective microorganism fermentation extract (EM-X) attenuates airway hyperreactivity and inflammation through selective inhibition of the TH2 response independently of antioxidant activity.

The effective microorganism fermentation extract (EM-X) is an antioxidant cocktail derived from the fermentation of plant material with effective microorganisms, and its clinical application is being increasingly scrutinized. In the current study, the antiasthmatic effect of EM-X was investigated using a mouse model. Inhalation of EM-X during OVA challenge resulted in a significant reduction in airway hyperreactivity (AHR) and airway recruitment of leukocytes including eosinophils. However, the level of 8-isoprostane in bronchoalveolar lavage fluid (BALF), a marker of oxidative stress in asthmatic patients, was unaltered by EM-X inhalation. Instead, ELISA data showed that levels of IL-4, IL-5 and IL-13 in BALF or lung tissues were significantly lower in EM-X-inhaling mice than in the control mice, but not the IFN-gamma level. A considerably lower amount of Ag-specific IgE and IgG1 was detected in the serum of EM-X-inhaling mice than in the serum of the controls, whereas their IgG2a secretion was similar. In addition, Ag-specific ex vivo IL-4, IL-5 and IL-13 production of draining lymph node cells was markedly diminished by EM-X inhalation, but not IFN-gamma. These data clearly show that inhaled EM-X suppresses type 2 helper T (TH2), but not type 1 helper T (TH1), response. In conclusion, inhalation of EM-X attenuates AHR and airway inflammation which results from selective inhibition of the TH2 response to allergen, but independently of antioxidant activity. Our data also suggest that EM-X may be effectively applied for control of allergic asthma.

Antiasthmatic activity and selective inhibition of type 2 helper T cell response by aqueous extract of semen armeniacae amarum.

Semen armeniacae amarum (SAA) has long been used to control asthma in Korean traditional medicine. However, its antiasthmatic action still remains poorly understood. In the current study, effective mechanism of SAA was investigated in a mouse model of allergic asthma induced by repeated sensitization and intranasal challenge with OVA. Airway hyperreactivity (AHR) measured by beta-methacholine-induced airflow obstruction and airway recruitment of leukocytes including eosinophils were significantly reduced by oral treatment of SAA water extract. Level of interleukin (IL)-4, but not Interferon gamma (IFN-gamma), in the bronchoalveolar lavage fluid (BALF) also appeared considerably lower in SAA-treated mice than in controls. Collectively, these data show that SAA suppresses type 2 helper T cell (Th2), but not type 1 helper T cell (Th1), response. This hypothesis was supported further by the data of ex vivo cytokine production of peribronchial lymph node cells. Thus, oral administration of SAA attenuates asthmatic manifestations including AHR and airway inflammation, which possibly result from selective inhibition of Th2 response to allergen. Our data strongly suggest that SAA may be effectively applied to control other Th2-related diseases as well as allergic asthma.