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Dendritic cells (DC) are potent antigen-presenting cells that can present tumor antigens chaperoned by heat shock proteins (HSPs), while local hyperthermia (LHT) can increase the expression of HSPs. In this study, we determine if intratumoral injection of immature DC after LHT (LHT1IT-DC) induces systemic antitumor immunity in patients with advanced melanoma, and investigate the potential immunological mechanisms involved in the treatments. Patients were randomly assigned to intratumoral administration of autologous immature DC triweekly, with (LHT1IT-DC, arm A, n 5 9) or without (IT-DC, arm B, n 5 9) LHT. Our results showed that there were no grade 3/4 toxicities. The time to progress (TTP) of arm A was 5 months, significantly longer than that in arm B (2 months, p < 0.05). However, the overall survival time had no statistical difference (13 months vs. 6 months, p > 0.05) between the 2 groups. Our ELISPOT assay showed a significantly increased melanoma-specific IFN-c production in arm A, suggesting that LHT1IT-DC was more effective in the induction of cytotoxic T lymphocytes (CTL) than IT-DC alone. Furthermore, we detected an increased HSPs expression 4 hr after the first LHT, an enhanced Th1/Th2 chemokines production 24 hr after the first LHT1IT-DC treatment, a promoted migration of DC to afferent lymph nodes, and a decreased infiltration of regulatory T cells (CD4 1 CD25 1) and an increased infiltration of active CTL (CD8 1 CD28 1 ) 48 hr after the third DC injection in arm A patients. Therefore, LHT1IT-DC can induce effective specific antitumor immunity and facilitate a Th1-polarized immune response in patients with advanced melanoma. ' 2007 Wiley-Liss, Inc.Key words: dendritic cell; hyperthermia; melanoma; chemokine; heat shock protein; Treg; antitumor immunity Dendritic cells (DC) -based immunotherapy has been shown to be one of the effective and promising strategies to overcome tumor-induced immunosuppression and induce tumor-specific immunity.1 DC are bone marrow-derived antigen presenting cells (APCs) that play a critical role in the induction and regulation of immune responses.2 DC are highly specialized professional APCs with potent capacity to capture and process antigens in the peripheral blood and tissues, and they subsequently migrate to draining lymph nodes where they present antigens to resting lymphocytes. 3 Key elements affect the efficacy of DC-based vaccines in vivo include loading DC with tumor antigens, maturation status of DC, migration of DC to secondary lymphoid organs and the immunization routes.3,4 For immunotherapy, tumor antigens are provided to DC in different forms such as incubating DC with synthetic or native peptides, tumor tissue lysates, purified proteins, tumorderived total RNA or by fusing malignant cells and DC.5-9 However, in certain cases it is difficult to obtain tumor specimen and identify tumor-associated antigens (TAA) or tumor-specific antigens (TSA) in some patients with malignant cancers. Therefore, intratumoral injection of immature DC in situ without loading DC ...

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The effects of resveratrol (RES)-loaded whey protein isolate (WPI)-dextran nanocomplex on the physicochemical stability of β-carotene (BC) emulsions were evaluated. WPI-dextran was prepared by Maillard-based glycation and confirmed with gel electrophoresis and OPA assay. WPI-RES and WPI-dextran-RES nanoparticles were prepared with a simple nanocomplexation protocol. Fluorescence spectra indicated that hydrophobic interaction was the main driving force for the WPI-dextran-RES nanocomplex. Spherical and uniformly dispersed structures as well as nanoscale Z-average size (<100 nm) were confirmed for WPI-RES and WPI-dextran-RES nanocomplex with DLS and TEM. The Z-average diameter of emulsions with WPI-dextran conjugate was remarkably lower than that with WPI. Environmental stress (ionic strength, heat, and pH) and storage stability were pronouncedly improved. The chemical stability of BC with WPI-dextran-RES and WPI-RES was also remarkably enhanced when exposed to UV light and thermal treatment. The advantages of the WPI-dextran-RES colloidal complex may provide a better alternative to effectively protect and deliver hydrophobic nutraceuticals.

The health-promoting benefits of resveratrol (RES) have attracted significant attention. Poor water solubility and chemical stability, however, hindered its application. In this study, α-lactalbumin (ALA)-RES nanoparticles were prepared by a simple nanocomplexation protocol. The particle sizes of ALA and the ALA-RES complex were 87.8, and 95.3 nm, respectively. AFM confirmed that both nanoparticles were spherical. XRD results confirmed that RES in ALA nanoparticles was amorphous. Fluorescence spectroscopy and FTIR showed that the ALA-RES nanocomplex was formed mainly by hydrophobic interactions. The water solubility increased by 32 times, compared to that of free RES. ALA nanocomplexation also appreciably improved the chemical stability of RES under all storage conditions, especially at pH 8.0 and high temperature. The ALA-RES nanocomplex showed significantly higher in vitro antioxidant activity than free RES. The results showed that the simple ALA-RES nanocomplex has the potential to be used as an effective antioxidant. The information obtained may enable the expanded application of ALA as an effective nanoscale carrier for delivering RES or other lipophilic nutraceuticals in the functional food, biomedical, and pharmaceutical products.