Clinical Applications of Natural Killer Cells

Natural killer (NK) cells are an essential component of the innate immune system, and they play a crucial role in immunity against malignancies. Recent advances in our understanding of NK cell biology have paved the way for new therapeutic strategies based on NK cells for the treatment of various cancers. In this section, we will focus on NK cell immunotherapy, including the enhancement of antibody‐dependent cellular cytotoxicity, the manipulation of receptor‐mediated activation, inclusion criteria based on killer cell immunoglobulin‐like receptor (KIR) ligand mismatches, and adoptive immunotherapy with ex vivo expanded chimeric antigen receptor (CAR)‐engineered or engager‐modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack any recipient tissues based on allogeneic human leukocyte antigens (HLAs), suggesting that NK‐mediated antitumor effects may be achieved without the risk of graft‐versus‐host disease (GvHD). Despite reports of clinical efficacy, the application of NK cell immunotherapy is limited. Developing strategies for manipulating NK cell products, host factors, and tumor targets are thus current subjects of diligent study. Research into the biology of NK cells has indicated that NK cell immunotherapy has the potential to become the forefront of cancer immunotherapy in the coming years

A novel polyrotaxane-based intracellular delivery system for camptothecin: In vitro feasibility evaluation

Camptothecin (CPT) is a naturally occurring alkaloid that shows promise in antitumor activity in vitro against various tumor cell lines. Its potential clinical uses, however, are hindered by a lack of reaction selectivity and poor water solubility. Presented herein is a novel polyrotaxane (PR)-based delivery system that could potentially lead to a highly effective yet less toxic CPT therapy. The approach involves the synthesis of the PR–CPT conjugates via hydrolyzable linkages. To enhance the therapeutic efficacy of CPT, a cell-penetrating peptide, LMWP, is linked to the conjugate to allow specific, intratumoral delivery of CPT. To avoid nonselective uptake of the conjugates by normal tissues following administration, the cell-penetrating function of LMWP on the conjugates is masked by heparin binding. This system was designed such that after accumulation at the tumor via the enhanced permeability and retention (EPR) effect, protamine can be subsequently administered to unmask heparin inhibition on LMWP, permitting intracellular uptake of the LMWP–PR–CPT conjugates. Once inside the tumor, CPT molecules are detached from the PR chain by hydrolysis, yielding a sustained concentration of CPT within tumor cells. In this paper, we demonstrated the in vitro feasibility of this delivery system. The LMWP–PR–CPT conjugates yielded a sevenfold increase in the overall CPT solubility, as well as a sustained release of CPT over a period of more than 7 days. Intracellular uptake of these conjugates by A2780 human ovarian cancer cells and regulation of such uptake by heparin and protamine were tested by MTT assay and confocal/flow cytometric methods, respectively. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57404/1/31452_ftp.pd

Effects of Zirconium Doping Into a Monoclinic Scheelite BiVO4 Crystal on Its Structural, Photocatalytic, and Photoelectrochemical Properties

Effects of zirconium (Zr) doping into BiVO4 powder on its structural properties and photocatalytic activity for O2 evolution were examined. The formation of BiVO4 powder crystallized in a monoclinic scheelite structure (ms-BiVO4) was achieved when the sample was doped with a relatively small amount of Zr. The photocatalytic activity of Zr-doped ms-BiVO4 powder was much higher than that of non-doped ms-BiVO4. However, further doping caused a reduction of photocatalytic activity for O2 evolution due to the occurrence of structural alterations into tetragonal scheelite and tetragonal zircon structures. Similar effects of Zr doping were also observed for the photoelectrochemical (PEC) system based on BiVO4 thin films doped with various amounts of Zr. Thus, Zr doping was confirmed to be effective for improvements of photocatalytic and PEC functions of BiVO4 for water oxidation

Amphiphilic γ-cyclodextrin–fullerene complexes with photodynamic activity

Amphiphilic γ-cyclodextrin–fullerene 2 : 1 complexes (CLFCH complexes) were prepared by high-speed vibration milling of lipophilic tail-grafted γ-cyclodextrin (γ-CD), hydrophilic tail-grafted γ-CD and fullerene C₆₀. The transamidation of γ-CD–fullerene complexes having two amino groups with lipophilic and hydrophilic activated esters also afforded amphiphilic CLFCH complexes. Self-assemblies consisting of amphiphilic CLFCH complexes efficiently generated singlet oxygen under photoirradiation. Under visible light irradiation conditions, CLFCH complexes bearing a vitamin E moiety as a lipophilic tail showed high photodynamic activity toward cancer cells

Characteristics and distribution of stone monuments at the Higashi-Hiroshima Campus of Hiroshima University

本研究では，広島大学東広島キャンパスを対象として，悉皆調査によりすべての石碑の分布や属性，特徴を明らかにすることで，石碑が有する文化的・歴史的価値を議論する契機となることを目的とした。調査の結果，147基の石碑を確認し，その分布は教育学部と工学部でそれぞれ4割に達し，学部の偏りが顕著であること，建立年代に着目すると，東広島キャンパスの移転前の石碑は103基と全体の約7割で，多くが移転前に建立されたことなどが明らかとなった。広島大学は，医学系学部・研究科・施設をのぞくすべての学部などが東広島キャンパスに移転すると同時に石碑も集まることになった。移設により元々建立された地から離れたことで建立当初の意義を失った側面もあるが，多数の石碑が一つのキャンパスに移設されたことで散逸を防ぎ，前身校から新制広島大学，そして統合移転から現在までの歴史を繋ぐ貴重な資料となり得ることが示唆された

Analysis for the units of regional geography on UK’s geography textbook: The case study of “Geog 4th edition”

In Britain, the volume of “Regional Geography” was decreased in “the National Curriculum”. The aim of this paper is to cralify the contents of “Regional Geography” in Britain. We analyzed the geographical school textbook “Geog 4th edition” by Oxfor University Press. We find that “Geog” has only 2 or 3 case studies in each grade. The students don’t learn all of the world in geographical class. That is because it is important to learn the geographical skill

Cytokine-Based Log-Scale Expansion of Functional Murine Dendritic Cells

BACKGROUND: Limitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies. METHODOLOGY/PRINCIPAL FINDINGS: Floating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines. CONCLUSIONS/SIGNIFICANCE: The concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy

Synthesis and characterization of polyurethanes crosslinked by polyrotaxanes consisting of half-methylated cyclodextrins and PEGs with different chain lengths

Three polyurethanes (PRX1500Me-PU, PRX4000Me-PU, and PRX6000Me-PU) crosslinked by polyrotaxanes (PRXs), which consist of half-methylated α-cyclodextrins (CyDs) and poly(oxyethylene)glycols with different chain lengths (PEG1500, PEG4000, and PEG6000), were synthesized. The filling ratios of CyD in PRX1500, PRX4000 and PRX6000 are 75, 63 and 37%, respectively. A polyurethane crosslinked by half-methylated CyD (CDMe-PU) was also prepared for comparison of their structure and properties. ATR-FT-IR spectra of the PUs showed that the formation ratio of hydrogen bond between the PU chains around PRXs increased with increase in the filling ratio. DSC and dynamic viscoelastic measurements and tensile tests for the PUs revealed that (i) reorganized-crystallization of the soft segment chains of PRX1500Me-PU easily occurred because of formation of a pure phase for them; (ii) the thermal and physical behaviors of PRX6000Me-PU are similar to those of CDMe-PU because CyDs as the crosslink points disperse in a similar fashion in the PUs; (iii) the PRX4000 with the moderate filling ratio of CyD in PRX4000Me-PU makes slow reorganized-crystallization of the soft segment chains in the PU as well as improves the tensile performance among the PUs