387 research outputs found

    Format blurring: how the advent of the Walmart Supercenter has changed the U.S. grocery industry

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    This paper develops a game-theoretic model that analyzes how a grocery store responds to the entry of a Walmart Supercenter using its store-format choice. By adopting a set of realistic assumptions, such as the cost advantage of Walmart and differentiated services of grocery stores, we find that the distance to a Walmart Supercenter is a key moderating factor in the store-format choice of grocery stores. Grocery stores would prefer to sell non-food items, but when sufficiently close to Walmart Supercenters they would specialise in food items, as consumers find it less costly to engage in two-stop shopping, making the gain from non-food items smaller. So an asymmetric equilibrium becomes feasible, wherein grocery stores carrying increasingly more non-food products and a new grocery store concept like Whole Foods and Wild Oats emphasising high-quality, organic foods can coexist. Our results yield important managerial implications. Under the specialisation strategy, the quality of its differentiated services should be sufficiently high, at least two to four times the disutility of two-stop shopping. Under the expansion strategy, grocery stores should engage in loss leadership, pricing non-food items below cost to lure large-basket consumers while earning higher margins from food items to compensate for the loss

    Poly(L-histidine)-tagged 5-aminolevulinic acid prodrugs: new photosensitizing precursors of protoporphyrin IX for photodynamic colon cancer therapy

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    Renjith P Johnson,1* Chung-Wook Chung,2* Young-Il Jeong,2 Dae Hwan Kang,2 Hongsuk Suh,3 Il Kim,11WCU Centre for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan, 2National Research and Development Center for Hepatobiliary Cancer, Pusan National University, Yangsan Hospital, Yangsan, Gyeongnam, 3Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Pusan, Korea*These authors contributed equally to this workBackground: 5-Aminolevulinic acid (ALA) and its derivatives have been widely used in photodynamic therapy. The main drawback associated with ALA-based photodynamic therapy (ALA-PDT) and ALA fluorescence diagnosis results from the hydrophilic nature of ALA and lack of selectivity for tumor versus nontumor cells. The application of certain triggers, such as pH, into conventional sensitizers for controllable 1O2 release is a promising strategy for tumor-targeted treatment.Methods: A series of pH-sensitive ALA-poly(L-histidine) [p(L-His)n] prodrugs were synthesized via ring opening polymerization of 1-benzyl-N-carboxy-L-histidine anhydride initiated by the amine hydrochloride group of ALA itself. As an alternative to ALA for PDT, the synthesized prodrugs were used to treat a cultured human colon cancer HCT116 cell line under different pH conditions. The effect of ALA-p(L-His)n derivatives was evaluated by monitoring the fluorescence intensity of protoporphyrin IX, and measuring the cell survival rate after suitable light irradiation.Results: The cytotoxicity and dark toxicity of ALA and synthesized ALA-p(L-His) derivatives in HEK293T and HCT116 cells in the absence of light at pH 7.4 and 6.8 shows that the cell viability was relatively higher than 100%. ALA-p(L-His)n showed high phototoxicity and selectivity in different pH conditions compared with ALA alone. Because the length of the histidine chain increases in the ALA-p(L-His)n prodrugs, the PDT effect was found to be more powerful. In particular, high phototoxicity was observed when the cells were treated with ALA-p(L-His)15, compared with treatment using ALA alone.Conclusion: The newly synthesized ALA-p(L-His)n derivatives are an effective alternative to ALA for enhancing protoporphyrin IX production and the selectivity of the phototoxic effect in tumor cells.Keywords: 5-aminolevulinic acid, photodynamic therapy, poly(L-histidine), bioconjugate, cancer cell

    Antitumor activity of sorafenib-incorporated nanoparticles of dextran/poly(dl-lactide-co-glycolide) block copolymer

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    Sorafenib-incoporated nanoparticles were prepared using a block copolymer that is composed of dextran and poly(DL-lactide-co-glycolide) [DexbLG] for antitumor drug delivery. Sorafenib-incorporated nanoparticles were prepared by a nanoprecipitation-dialysis method. Sorafenib-incorporated DexbLG nanoparticles were uniformly distributed in an aqueous solution regardless of the content of sorafenib. Transmission electron microscopy of the sorafenib-incorporated DexbLG nanoparticles revealed a spherical shape with a diameter < 300 nm. Sorafenib-incorporated DexbLG nanoparticles at a polymer/drug weight ratio of 40:5 showed a relatively uniform size and morphology. Higher initial drug feeding was associated with increased drug content in nanoparticles and in nanoparticle size. A drug release study revealed a decreased drug release rate with increasing drug content. In an in vitro anti-proliferation assay using human cholangiocarcinoma cells, sorafenib-incorporated DexbLG nanoparticles showed a similar antitumor activity as sorafenib. Sorafenib-incorporated DexbLG nanoparticles are promising candidates as vehicles for antitumor drug targeting

    Effect of 5-aminolevulinic acid-based photodynamic therapy via reactive oxygen species in human cholangiocarcinoma cells

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    Cancer cells have been reported to exhibit an enhanced capacity for protoporphyrin IX (PpIX) synthesis facilitated by the administration of 5-aminolevulinic acid (ALA). We investigated the effect of ALA-based photodynamic therapy (PDT) on human cholangiocarcinoma cells (HuCC-T1). Since protoporphyrin IX (PpIX), a metabolite of ALA, can produce reactive oxygen species (ROS) under irradiation and then induce phototoxicity, ALA-based PDT is a promising candidate for the treatment of cholangiocarcinoma. When various concentrations of ALA (0.05–2 mM) were used to treat HuCC-T1 cells for 6 or 24 hours, the intracellular PpIX level increased according to the ALA concentration and treatment time. Furthermore, an increased amount of PpIX in HuCC-T1 cells induced increased production of ROS by irradiation, resulting in increased phototoxicity

    Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

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    Young-Il Jeong1,*, Do Hyung Kim1,2,*, Chung-Wook Chung1, Jin-Ju Yoo1, Kyung Ha Choi1, Cy Hyun Kim1,2, Seung Hee Ha1, Dae Hwan Kang1,2 1National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, Research Institute for Convergence of Biomedical Science and Technology, 2School of Medicine, Pusan National University, Yangsan, Republic of Korea*These authors contributed equally to this work.Background: Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer.Methods: We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content. Results: During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin.Conclusion: DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.Keywords: dextran, polymeric micelle, block copolymer, poly(DL-lactide-co-glycolide

    Are Men Who Undergo Radical Prostatectomy with Lower Urinary Tract Symptoms at an Increased Risk for Aggressive Prostate Cancer?

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    PURPOSE: We aimed to determine whether prediagnostic lower urinary tract symptoms (LUTS) are associated with the aggressiveness of nonmetastatic prostate cancer (PCa) and compared the clinicopathologic features of PCa patients with and without preexisting LUTS. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 295 prostate cancer patients who underwent a radical prostatectomy (RP) by a single surgeon from 2006 to 2010. A total of 205 patients were assigned to two groups according to whether they showed preoperative LUTS (International Prostate Symptom Score [IPSS]> or =8). Clinical, operative, pathologic, and postoperative functional data were collected. RESULTS: The mean age at RP was 62.7 years in the no LUTS group (group A, n=108) and 64.7 in the LUTS group (group B, n=97). The baseline mean IPSS score was 6.1 in group A and 14.6 in group B (p=0.029). The incidence of pathologic T3a stage or above was significantly higher in group B than in group A (p=0.036). The mean postoperative follow-up period was 16.8 months (range, 4 to 38 months). The mean time to biochemical recurrence was 16.9 and 18.2 months in groups A and B, respectively (p=0.148). The median time to recovery of urinary incontinence was 3.6 and 3.3 months in groups A and B, respectively. CONCLUSIONS: PCa patients without baseline LUTS had a favorable result of pathologic T stage even though there were no significant differences in biochemical recurrence or recovery of postoperative incontinence compared with patients with baseline LUTS.ope
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